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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "medicine and health sciences", "diagnostic radiology", "ocular anatomy", "vertebrates", "social sciences", "neuroscience", "dogs", "animals", "mammals", "macular disorders", "animal models", "retinal disorders", "model organisms", "experimental organism systems", "eyes", "research and...	An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease	journal.pgen.1007873	null	[ [ "Inherited retinal dystrophies are a genetically and clinically heterogeneous group of eye diseases leading to severe visual impairment in both humans and dogs [1–6] .", "These diseases include various forms of retinitis pigmentosa ( RP ) , Leber congenital amaurosis ( LCA ) , age-related macular degenera...	[ "Autosomal recessive retinal degenerative diseases cause visual impairment and blindness in both humans and dogs .", "Currently , no standard treatment is available , but pioneering gene therapy-based canine models have been instrumental for clinical trials in humans .", "To study a novel form of retinal degene...	[ "Stargardt disease ( STGD ) is the most common inherited retinal disease causing visual impairment and blindness in children and young adults , affecting 1 in 8–10 thousand people .", "For other inherited retinal diseases , the dog has become an established comparative animal model , both for identifying the unde...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/protozoal infections", "molecular biology/nucleolus and nuclear bodies", "molecular biology/chromatin structure" ]	A Novel Toxoplasma gondii Nuclear Factor TgNF3 Is a Dynamic Chromatin-Associated Component, Modulator of Nucleolar Architecture and Parasite Virulence	journal.ppat.1001328	null	[ [ "Toxoplasma gondii has long been a major medical and veterinary problem capable of causing abortion , or congenital birth defects in both humans and livestock .", "The advent of AIDS has drawn even more attention to T . gondii as a serious opportunistic pathogen .", "T . gondii is distinct from nearly...	[ "In Toxoplasma gondii , cis-acting elements present in promoter sequences of genes that are stage-specifically regulated have been described .", "However , the nuclear factors that bind to these cis-acting elements and regulate promoter activities have not been identified .", "In the present study , we performe...	[ "Apicomplexa including Toxoplasma gondii are responsible for a variety of deadly infections .", "These intracellular parasites have complex life cycles within different hosts and their infectivity relies on their capacity to regulate gene expression in response to different environments .", "However , to date ,...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "medicine", "immune cells", "immunology", "host-pathogen interaction", "microbiology", "bacterial diseases", "emerging infectious diseases", "immunologic techniques", "immunomodulation", "infectious diseases", "microbial pathogens", "biology", "pathogenesis", "immune resp...	B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response	journal.ppat.1003472	null	[ [ "It has recently been demonstrated that B cells can shape the development of the immune response to Mycobacterium tuberculosis [1] , [2] .", "The lungs of M . tuberculosis-infected B cell-deficient mice display exacerbated inflammation , with enhanced neutrophil recruitment [1] .", "Neutrophils are am...	[ "We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis , including the level of neutrophil infiltration and granulomatous inflammation at the site of infection .", "The present study examined the mechanisms by which B cells regulate the host neutrophilic response...	[ "Mycobacterium tuberculosis poses a serious threat to public health globally .", "It has been well established that T cells are critical in protection against M . tuberculosis .", "The role of B cells and humoral immunity in the process is less well understood .", "We previously showed that B cells and humora...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "engineering and technology", "geographical locations", "uganda", "cell phones", "pediatrics", "research design", "surveys", "infectious disease control", "africa", "research and analysis methods", "infectious diseases", "computer and information sciences", ...	A real-time medical cartography of epidemic disease (Nodding syndrome) using village-based lay mHealth reporters	journal.pntd.0006588	null	[ [ "Disease outbreaks in remote rural populations of Africa and elsewhere are often detected late by public health entities .", "Reasons include dependence on traditional remedies and healers , low village literacy and knowledge of how to report a disease outbreak , lack of distributed health professionals ,...	[ "Disease surveillance in rural regions of many countries is poor , such that prolonged delays ( months ) may intervene between appearance of disease and its recognition by public health authorities .", "For infectious disorders , delayed recognition and intervention enables uncontrolled disease spread .", "We t...	[ "Absence of health monitoring of rural populations in low-income countries allows diseases to emerge and spread for months before their detection by public health authorities .", "We tested the feasibility of using smartphones operated by lay villagers to report health information in real time from the population...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "engineering and technology", "cloning", "cell disruption", "animals", "notch signaling", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "experimental organism systems", "molecular biology techniques", ...	Notch-dependent epithelial fold determines boundary formation between developmental fields in the Drosophila antenna	journal.pgen.1006898	null	[ [ "During development , an organism is progressively divided into discrete fields that develop into different organs or parts of an organ .", "In many cases , the adjacent developmental fields develop distinct morphological , functional and molecular characteristics and are often divided by a sharp boundary...	[ "Compartment boundary formation plays an important role in development by separating adjacent developmental fields .", "Drosophila imaginal discs have proven valuable for studying the mechanisms of boundary formation .", "We studied the boundary separating the proximal A1 segment and the distal segments , defin...	[ "During development , boundary formation between adjacent developmental fields is important to maintain the integrity of complex organs and tissues .", "We examined how boundaries become established between adjacent developmental fields—which are defined by expression of distinct selector genes and developmental ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "computer science", "genetics", "biology", "computational biology", "computerized simulations", "gene networks" ]	Constraint and Contingency in Multifunctional Gene Regulatory Circuits	journal.pcbi.1003071	null	[ [ "Gene regulatory circuits are at the heart of many fundamental biological processes , ranging from developmental patterning in multicellular organisms [1] to chemotaxis in bacteria [2] .", "Regulatory circuits are usually multifunctional .", "This means that they can form different metastable gene exp...	[ "Gene regulatory circuits drive the development , physiology , and behavior of organisms from bacteria to humans .", "The phenotypes or functions of such circuits are embodied in the gene expression patterns they form .", "Regulatory circuits are typically multifunctional , forming distinct gene expression patt...	[ "Many essential biological processes , ranging from embryonic patterning to circadian rhythms , are driven by gene regulatory circuits , which comprise small sets of genes that turn each other on or off to form a distinct pattern of gene expression .", "Gene regulatory circuits often have multiple functions .", ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology", "computational biology", "biophysics" ]	Mutation D816V Alters the Internal Structure and Dynamics of c-KIT Receptor Cytoplasmic Region: Implications for Dimerization and Activation Mechanisms	journal.pcbi.1002068	null	[ [ "Regulation of physiological functions in the cell is mostly governed by phosphorylation – a crucial mechanism in cell signaling – catalyzed by protein kinases [1]–[5] .", "Stem cell factor ( SCF ) receptor or CD117 , also known as human receptor tyrosine kinase ( RTK ) KIT ( according to the nomenclature...	[ "The type III receptor tyrosine kinase ( RTK ) KIT plays a crucial role in the transmission of cellular signals through phosphorylation events that are associated with a switching of the protein conformation between inactive and active states .", "D816V KIT mutation is associated with various pathologies includin...	[ "Protein kinases are involved in a huge amount of cellular processes through phosphorylation , a crucial mechanism in cell signaling , and their misregulation often results in disease .", "The deactivation of protein tyrosine kinases ( PTKs ) or their oncogenic activation arises from mutations which affect the pr...	2011
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "systems biology", "biology", "computational biology" ]	Multi-study Integration of Brain Cancer Transcriptomes Reveals Organ-Level Molecular Signatures	journal.pcbi.1003148	null	[ [ "One important goal in systems medicine is to develop molecular diagnostics that can accurately and comprehensively report health and disease states of an organ system [1] , [2] .", "The discovery of organ-level molecular signatures [3] from global biomolecule expression measurements would mark a signific...	[ "We utilized abundant transcriptomic data for the primary classes of brain cancers to study the feasibility of separating all of these diseases simultaneously based on molecular data alone .", "These signatures were based on a new method reported herein – Identification of Structured Signatures and Classifiers ( ...	[ "From a multi-study , integrated transcriptomic dataset , we identified a marker panel for differentiating major human brain cancers at the gene-expression level .", "The ISSAC molecular signatures for brain cancers , composed of 44 unique genes , are based on comparing expression levels of pairs of genes , and p...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Recent Emergence and Spread of an Arctic-Related Phylogenetic Lineage of Rabies Virus in Nepal	journal.pntd.0002560	null	[ [ "Rabies virus ( RABV ) is the prototype species of the genus Lyssavirus , in the family Rhabdoviridae [1] .", "Members of this viral genus encompass single-stranded , negative sense viruses with a genome size of nearly 12 kb .", "Among the 12 species of lyssaviruses identified to date , RABV has the b...	[ "Rabies is a zoonotic disease that is endemic in many parts of the developing world , especially in Africa and Asia .", "However its epidemiology remains largely unappreciated in much of these regions , such as in Nepal , where limited information is available about the spatiotemporal dynamics of the main etiolog...	[ "Rabies is endemic in most Asian countries and represents a serious public health issue , with an estimated 31 , 000 people dying each year of this disease .", "The majority of human cases are transmitted by domestic dogs , which act as the principal reservoir host and vector .", "However , molecular epidemiolo...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/microbial growth and development", "molecular biology/post-translational regulation of gene expression", "microbiology/microbial growth and development", "biochemistry/protein chemistry" ]	Role of Individual Subunits of the Neurospora crassa CSN Complex in Regulation of Deneddylation and Stability of Cullin Proteins	journal.pgen.1001232	null	[ [ "The Cop9 signalosome ( CSN ) is a multiprotein complex that was initially discovered in Arabidopsis thaliana as an important regulator of photomorphogenesis , and was later found to participate in a wide range of processes in eukaryotes [1] .", "The CSN usually contains eight subunits ( CSN1–CSN8 ) in hi...	[ "The Cop9 signalosome ( CSN ) is an evolutionarily conserved multifunctional complex that controls ubiquitin-dependent protein degradation in eukaryotes .", "We found seven CSN subunits in Neurospora crassa in a previous study , but only one subunit , CSN-2 , was functionally characterized .", "In this study , ...	[ "Protein degradation is precisely controlled in cells .", "The ubiquitin-mediated protein degradation pathway is highly conserved in eukaryotes , and the activity of ubiquitin ligases is regulated by the Cop9 signalosome ( CSN ) , a multisubunit complex that is evolutionarily conserved from yeast to humans .", ...	2010
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND)	journal.pgen.1005352	null	[ [ "Diabetic kidney disease ( DKD ) is a devastating complication in patients with diabetes mellitus ( DM ) and is associated with high risk for cardiovascular disease and death . [1 , 2]", "DKD is the leading cause of end-stage kidney disease ( ESKD ) requiring renal replacement therapy in developed nations...	[ "Diabetic kidney disease ( DKD ) is the most common etiology of chronic kidney disease ( CKD ) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus .", "Approximately 45% of U . S . patients with incident end-stage kidney disease ( ESKD ) have DKD .", "Ind...	[ "Type 2 diabetes is the most common cause of severe kidney disease worldwide and diabetic kidney disease ( DKD ) associates with premature death .", "Individuals of non-European ancestry have the highest burden of type 2 DKD; hence understanding the causes of DKD remains critical to reducing health disparities ."...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "meiosis", "plant biology", "centromeres", "plant science", "model organisms", "epigenetics", "linkage (genetics)", "chromatin", "arabidopsis thaliana", "chromosomal inheritance", "chromosome biology", "plant genetics", "biology", "dna modification", "plant and algal models", "heredity...	Epigenetic Remodeling of Meiotic Crossover Frequency in Arabidopsis thaliana DNA Methyltransferase Mutants	journal.pgen.1002844	null	[ [ "During meiosis homologous chromosomes pair and undergo reciprocal exchange , to produce crossovers ( COs ) .", "COs are initiated by SPO11-catalyzed DNA double strand breaks ( DSBs ) , which are resected to generate single-stranded 3′ tails on either side of the break ( ssDNA ) [1] .", "The ssDNA can...	[ "Meiosis is a specialized eukaryotic cell division that generates haploid gametes required for sexual reproduction .", "During meiosis , homologous chromosomes pair and undergo reciprocal genetic exchange , termed crossover ( CO ) .", "Meiotic CO frequency varies along the physical length of chromosomes and is ...	[ "The majority of eukaryotes reproduce via a specialized cell division called meiosis , which generates gametes with half the number of chromosomes .", "During meiosis , homologous chromosomes pair and undergo a process of reciprocal exchange , called crossing-over ( CO ) , which generates new combinations of gene...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "genetics", "biology", "evolutionary biology", "genetics and genomics" ]	Distinct Molecular Strategies for Hox-Mediated Limb Suppression in Drosophila: From Cooperativity to Dispensability/Antagonism in TALE Partnership	journal.pgen.1003307	null	[ [ "Hox genes encode homeodomain ( HD ) containing transcription factors widely used for diversifying animal body plans in development and evolution [1]–[3] .", "The Hox gene repertoire most likely arose from tandem duplication events of ancestral genes , followed by sequence divergence that promoted the eme...	[ "The emergence following gene duplication of a large repertoire of Hox paralogue proteins underlies the importance taken by Hox proteins in controlling animal body plans in development and evolution .", "Sequence divergence of paralogous proteins accounts for functional specialization , promoting axial morphologi...	[ "Animal body plan diversity is controlled by transcription factors that select within each cell of a multi-cellular organism the set of genes to be expressed , eventually allowing distinct fate to emerge according to spatial coordinates .", "Transcription factors can be grouped based on their DNA binding domains ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "tube morphogenesis", "morphogenesis", "biology and life sciences", "developmental biology" ]	Epidermal Growth Factor Signalling Controls Myosin II Planar Polarity to Orchestrate Convergent Extension Movements during Drosophila Tubulogenesis	journal.pbio.1002013	A study in fruit flies shows that during the elongation of embryonic renal tubules, graded signalling provides axial information for polarized myosin pulses that shorten cells circumferentially, driving intercalation of the cells and elongation of the tubule.	[ [ "Our tissues and organs are built up around arrays of tubes that allow the exchange of nutrients , ions , and gases vital for bodily function .", "These tubules have precise architectures tailored to their physiological activities .", "It is important that appropriate tubule dimensions are established...	[ "Most epithelial tubes arise as small buds and elongate by regulated morphogenetic processes including oriented cell division , cell rearrangements , and changes in cell shape .", "Through live analysis of Drosophila renal tubule morphogenesis we show that tissue elongation results from polarised cell intercalati...	[ "Many of the tissues in our bodies are built up around complex arrays of elongated cellular tubes , which permit the entry , exit , and transport of essential molecules such as oxygen , glucose , and water .", "These tubes often arise as short buds , which elongate dramatically as the organ grows .", "We sought...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "phosphorylation", "oxidative stress", "messenger rna", "dna-binding proteins", "microbiology", "parasitic protozoans", "protozoan life cycles", "developmental biology", "trypomastigotes", "protozoans", "polymerases", "dna", "epimastigotes", "proteins", "life cycles", "biochemistry", ...	Endogenous overexpression of an active phosphorylated form of DNA polymerase β under oxidative stress in Trypanosoma cruzi	journal.pntd.0006220	null	[ [ "Trypanosoma cruzi , a flagellated protozoan , is the causative agent of Chagas´ disease ( CD ) , which constitutes a major public health problem in Latin America .", "In endemic regions 10 million people are infected by the parasite and another 25 million are at risk of acquiring the infection [1] .", ...	[ "Trypanosoma cruzi is exposed during its life to exogenous and endogenous oxidative stress , leading to damage of several macromolecules such as DNA .", "There are many DNA repair pathways in the nucleus and mitochondria ( kinetoplast ) , where specific protein complexes detect and eliminate damage to DNA .", "...	[ "Exposure of Trypanosome cruzi to oxidative stress leads to damage of several macromolecules such as DNA .", "DNA polymerases play a very important role in DNA repair after oxidative damage .", "One of them is Tc DNA polymerase β .", "In this work , two form of this DNA polymerase were identified and overexpr...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Virulence of Group A Streptococci Is Enhanced by Human Complement Inhibitors	journal.ppat.1005043	null	[ [ "Streptococcus pyogenes , also known as Group A Streptococcus ( GAS ) is an important human bacterial pathogen that is widespread and responsible for more than 700 million infections globally each year [1] .", "GAS causes a spectrum of diseases , ranging from milder pharyngitis and superficial skin infect...	[ "Streptococcus pyogenes , also known as Group A Streptococcus ( GAS ) , is an important human bacterial pathogen that can cause invasive infections .", "Once it colonizes its exclusively human host , GAS needs to surmount numerous innate immune defense mechanisms , including opsonization by complement and consequ...	[ "Streptococcus pyogenes is an important cause of human infections worldwide , ranging from mild and superficial disease to life-threatening invasive infections .", "Development of new and efficient therapies for infections requires animal models that faithfully recapitulate infection in humans .", "Humans are t...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biophysics", "eubacteria", "computational biology" ]	Stereochemical Criteria for Prediction of the Effects of Proline Mutations on Protein Stability	journal.pcbi.0030241	null	[ [ "Proline ( Pro ) is unique among the 20 naturally occurring amino acid residues .", "On the one hand , because Pro lacks an amide proton the main chain amide N is incapable of forming H-bonds ( hydrogen bonds ) .", "Hence , substituting a residue involved in a main chain H-bond with Pro could destabil...	[ "When incorporated into a polypeptide chain , proline ( Pro ) differs from all other naturally occurring amino acid residues in two important respects .", "The φ dihedral angle of Pro is constrained to values close to −65° and Pro lacks an amide hydrogen .", "Consequently , mutations which result in introductio...	[ "Unlike other amino acids that constitute proteins , Proline is missing a vital hydrogen atom and also bestows local structural rigidity to the three-dimensional ( 3D ) structure of proteins .", "In some locations , proline can be introduced with little or no detrimental effect to protein function , while at othe...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immunology/cellular microbiology and pathogenesis" ]	Analysis of Antibody and Cytokine Markers for Leprosy Nerve Damage and Reactions in the INFIR Cohort in India	journal.pntd.0000977	null	[ [ "Leprosy is a chronic granulomatous disease affecting skin and nerve .", "There is a range of clinical and immunological responses to infection with Mycobacterium leprae and the disease manifests as a spectrum .", "At the tuberculoid end of the spectrum there is a well developed immune response and my...	[ "The ILEP Nerve Function Impairment in Reaction ( INFIR ) is a cohort study designed to identify predictors of reactions and nerve function impairment ( NFI ) in leprosy .", "Antibodies to mycobacteria , nerve components and serum cytokine were measured as potential markers for their possible association with rea...	[ "Leprosy is one of the oldest known diseases .", "In spite of the established fact that it is least infectious and a completely curable disease , the social stigma associated with it still lingers in many countries and remains a major obstacle to self reporting and early treatment .", "The nerve damage that occ...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "medicinal chemistry", "african trypanosomiasis", "parasitic diseases", "neglected tropical diseases", "protein kinase signaling cascade", "infectious diseases", "chemistry", "biology", "molecular biology", "signal transduction", "chagas disease", "leishmaniasis", "molecular ce...	The Susceptibility of Trypanosomatid Pathogens to PI3/mTOR Kinase Inhibitors Affords a New Opportunity for Drug Repurposing	journal.pntd.0001297	null	[ [ "The pathogenic protozoans Leishmania major , L . donovani , Trypanosoma brucei , and T . cruzi are the causative agents for a collection of diseases that primarily affect the developing world , and are potentially lethal when untreated .", "Taken together , visceral and cutaneous leishmaniases , human Af...	[ "Target repurposing utilizes knowledge of “druggable” targets obtained in one organism and exploits this information to pursue new potential drug targets in other organisms .", "Here we describe such studies to evaluate whether inhibitors targeting the kinase domain of the mammalian Target of Rapamycin ( mTOR ) a...	[ "In our study we describe the potency of established phosphoinositide-3-kinase ( PI3K ) and mammalian Target of Rapamycin ( mTOR ) kinase inhibitors against three trypanosomatid parasites: Trypanosoma brucei , T . cruzi , and Leishmania sp .", ", which are the causative agents for African sleeping sickness , Chag...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cellular stress responses", "signaling networks", "mathematics", "stress signaling cascade", "regulatory networks", "biology", "nonlinear dynamics", "systems biology", "biochemical simulations", "signal transduction", "cell biology", "computational biology", "molecular cell biology", "sig...	A Protein Turnover Signaling Motif Controls the Stimulus-Sensitivity of Stress Response Pathways	journal.pcbi.1002932	null	[ [ "Eukaryotic cells must constantly recycle their proteomes .", "Of the approximately 109 proteins in a typical mouse L929 fibrosarcoma cell , 106 are degraded every minute [1] .", "Assuming first-order degradation kinetics , this rate of constitutive protein turnover , or flux , imposes an average half...	[ "Stimulus-induced perturbations from the steady state are a hallmark of signal transduction .", "In some signaling modules , the steady state is characterized by rapid synthesis and degradation of signaling proteins .", "Conspicuous among these are the p53 tumor suppressor , its negative regulator Mdm2 , and th...	[ "Eukaryotic cells constantly synthesize new proteins and degrade old ones .", "While most proteins are degraded within 24 hours of being synthesized , some proteins are short-lived and exist for only minutes .", "Using mathematical models , we asked how rapid turnover , or flux , of signaling proteins might reg...	2013
[ "Introduction", "Results/Discussion", "Conclusion", "Methods" ]	[ "africans", "linguistics", "population genetics", "geographical locations", "sudan", "social sciences", "south sudan", "sociolinguistics", "ethnicities", "population biology", "africa", "homozygosity", "people and places", "languages", "heredity", "genetics", "biology and life scienc...	Northeast African genomic variation shaped by the continuity of indigenous groups and Eurasian migrations	journal.pgen.1006976	null	[ [ "The Nile River Valley and northeast Africa have experienced a long history of human habitation .", "The region harbored some of the most ancient civilizations in the world and contains fossil finds of the earliest anatomically modern humans [1–3] .", "Agriculture has a long history in the Nile River ...	[ "Northeast Africa has a long history of human habitation , with fossil-finds from the earliest anatomically modern humans , and housing ancient civilizations .", "The region is also the gate-way out of Africa , as well as a portal for migration into Africa from Eurasia via the Middle East and the Arabian Peninsul...	[ "Northeast Africa has geographic and historical links to Eurasia via the Middle East and the Arabian Peninsula , but the demographic history of the region itself has been more elusive .", "We investigate genomic diversity of northeast African populations and found a clear bimodal distribution of variation , corre...	2017
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biochemistry", "biophysics/structural genomics", "biophysics/biomacromolecule-ligand interactions", "biochemistry/structural genomics", "biophysics" ]	Structural and Biochemical Characterization of the Human Cyclophilin Family of Peptidyl-Prolyl Isomerases	journal.pbio.1000439	null	[ [ "Cyclophilins are peptidyl-prolyl isomerases ( PPIases: EC 5 . 2 . 1 . 8 ) and are characterized by their ability to catalyze the interconversion of cis and trans isomers of proline [1] .", "Cyclophilins and the structurally unrelated FK506 binding proteins were initially described as the in vivo receptor...	[ "This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3-D representations and animated transitions .", "Please note that a Web plugin is required to access this enhanced functionality .", "Instructions for the installation and use of the web plug...	[ "Cyclophilins are proteins that catalyze the isomerization of prolines , interconverting this structurally important amino acid between cis and trans isomers .", "Although there are 17 cyclophilins in the human genome , the function of most cyclophilin isoforms is unknown .", "At least some members of this prot...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "medicine and health sciences", "pathology and laboratory medicine", "gene regulation", "bacillus", "microbiology", "prokaryotic models", "model organisms", "molecular genetics", "bacterial pathogens", "research and analysis methods", "microbial physiology", "medical microbio...	Evidence of a Bacterial Receptor for Lysozyme: Binding of Lysozyme to the Anti-σ Factor RsiV Controls Activation of the ECF σ Factor σV	journal.pgen.1004643	null	[ [ "Cells respond to changes in their environments using signal transduction systems , which transmit information from outside the cell across the membrane to effect transcriptional responses .", "Regulated Intramembrane Proteolysis ( RIP ) is one mechanism by which cells sense and respond to changes in the ...	[ "σ factors endow RNA polymerase with promoter specificity in bacteria .", "Extra-Cytoplasmic Function ( ECF ) σ factors represent the largest and most diverse family of σ factors .", "Most ECF σ factors must be activated in response to an external signal .", "One mechanism of activation is the stepwise proteo...	[ "All cells sense and respond to changes in their environments by transmitting information across the membrane .", "In bacteria , σ factors provide promoter specificity to RNA polymerase .", "Bacteria encode Extra-Cytoplasmic Function ( ECF ) σ factors , which often respond to extracellular signals .", "Activa...	2014
[ "Introduction", "Methods", "Results", "Discussions" ]	[ "medicine and health sciences", "geographical locations", "tropical diseases", "parasitic diseases", "data management", "filariasis", "pharmaceutics", "neglected tropical diseases", "pharmacology", "lymphatic filariasis", "africa", "public and occupational health", "computer and information ...	Assessing Lymphatic Filariasis Data Quality in Endemic Communities in Ghana, Using the Neglected Tropical Diseases Data Quality Assessment Tool for Preventive Chemotherapy	journal.pntd.0004590	null	[ [ "The Global Programme to Eliminate Lymphatic Filariasis ( GPELF ) started its activities in the year 2000 , with the aims of eliminating lymphatic filariasis ( LF ) as a public health problem by the year 2020 , through mass drug administration ( MDA ) in endemic implementation units ( IU ) [1] .", "In man...	[ "The activities of the Global Programme for the Elimination of Lymphatic Filariasis have been in operation since the year 2000 , with Mass Drug Administration ( MDA ) undertaken yearly in disease endemic communities .", "Information collected during MDA–such as population demographics , age , sex , drugs used and...	[ "The Global Programme for the Elimination of Lymphatic Filariasis has been conducting yearly treatment of entire communities in endemic countries since the year 2000 .", "During the treatments various information is collected on the populations , number of medicine tablets distributed and remaining , the number o...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cardiovascular disorders/arrhythmias, electrophysiology, and pacing", "computational biology/systems biology", "physiology/cardiovascular physiology and circulation" ]	Regression Analysis for Constraining Free Parameters in Electrophysiological Models of Cardiac Cells	journal.pcbi.1000914	null	[ [ "Mathematical modeling has become an increasingly popular and important technique for gaining insight into biological systems , both in physiology , where models have a long history [1] , [2] , and in biochemistry and cell biology , where quantitative approaches have gained traction more recently [3] , [4] ."...	[ "A major challenge in computational biology is constraining free parameters in mathematical models .", "Adjusting a parameter to make a given model output more realistic sometimes has unexpected and undesirable effects on other model behaviors .", "Here , we extend a regression-based method for parameter sensit...	[ "Mathematical models of biological processes generally contain many free parameters that are not known from experiments .", "Choosing values for these parameters , although an important step in the construction of realistic computational models , is frequently performed using an ad hoc approach that is a combinat...	2010
[ "Introduction", "Result", "Discussion", "Materials and methods" ]	[ "blood cells", "body weight", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "animal models of disease", "immunology", "microbiology", "animal models", "viruses", "model organisms", "physiological parameters", "rna viruses", "experimenta...	ICR suckling mouse model of Zika virus infection for disease modeling and drug validation	journal.pntd.0006848	null	[ [ "Mosquito-borne Zika virus ( ZIKV ) , which belongs to the Flavivirus genus of the Flaviviridae family , is an emerging threat to human health worldwide [1] .", "The genome of ZIKV consists of a single-stranded positive sense RNA , which encodes a single polypeptide [2 , 3] .", "The single polypeptide...	[ "Zika virus ( ZIKV ) infection causes diseases ranging from acute self-limiting febrile illness to life-threatening Guillain–Barré Syndrome and other neurological disorders in adults .", "Cumulative evidence suggests an association between ZIKV infection and microcephaly in newborn infants .", "Given the host-r...	[ "Mosquito-borne Zika virus ( ZIKV ) is an emerging threat to human health worldwide .", "In 2007 , a ZIKV outbreak was reported in the Yap Island of Micronesia and was the first outbreak outside Africa and Asia .", "In 2013 and 2014 , another ZIKV outbreak was reported in French Polynesia , and more than 28 , 8...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Targeting Ergosterol Biosynthesis in Leishmania donovani: Essentiality of Sterol 14alpha-demethylase	journal.pntd.0003588	null	[ [ "Leishmania are vector-borne protozoan parasites .", "They have a digenetic lifecycle; promastigotes are transmitted by the sandfly vector to the mammalian host , where they are taken up by phagocytic cells and differentiate into the amastigote stage within the macrophage phagolysososme .", "Amastigot...	[ "Leishmania protozoan parasites ( Trypanosomatidae family ) are the causative agents of cutaneous , mucocutaneous and visceral leishmaniasis worldwide .", "While these diseases are associated with significant morbidity and mortality , there are few adequate treatments available .", "Sterol 14alpha-demethylase (...	[ "Visceral leishmaniasis is the second most lethal parasitic infection after malaria .", "Other forms of leishmaniasis also cause significant morbidity .", "However , there are few treatments available , and many cause severe side effects or are associated with the development of resistance .", "A key differen...	2015
[ "Introduction", "Results", "Ym1 during adaptive immunity is required for lung tissue repair", "Discussion", "Methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune physiology", "diagnostic radiology", "cytokines", "immune cells", "immunology", "parasitic diseases", "nematode infections", "physiological processes", "developmental biology", "molecular development", "research...	Ym1 induces RELMα and rescues IL-4Rα deficiency in lung repair during nematode infection	journal.ppat.1007423	null	[ [ "Type 2 immunity is an important component of host defense against helminth infections [1] .", "Murine infection with the lung migrating nematode , Nippostrongylus brasiliensis , elicits a strongly polarised type 2 response , characterised by IL-4 , IL-13 , IL-5 and IL-9 cytokines .", "This response i...	[ "Ym1 and RELMα are established effector molecules closely synonymous with Th2-type inflammation and associated pathology .", "Here , we show that whilst largely dependent on IL-4Rα signaling during a type 2 response , Ym1 and RELMα also have IL-4Rα-independent expression patterns in the lung .", "Notably , we f...	[ "Immune cells produce molecules that limit infections , attract other immune cells or repair tissue damage .", "Two such molecules , Ym1 and RELMα , are abundantly produced in mice during infection and injury .", "Related human molecules are strongly associated with many chronic diseases and yet we know very li...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "theoretical biology", "biology" ]	How Landscape Heterogeneity Frames Optimal Diffusivity in Searching Processes	journal.pcbi.1002233	null	[ [ "The random search problem has lately received a great deal of attention [1] , [2] .", "This is partly due to its broad interdisciplinary range of applications , which include , e . g . , enhanced diffusion of regulatory proteins while “searching” for specific DNA spots [3] , [4] and the finding of bindin...	[ "Theoretical and empirical investigations of search strategies typically have failed to distinguish the distinct roles played by density versus patchiness of resources .", "It is well known that motility and diffusivity of organisms often increase in environments with low density of resources , but thus far there...	[ "Understanding how animals search for food is crucial for animal ecology .", "Although much has been learned about the main aspects of the so-called foraging problem , some important questions still remain unanswered .", "In this work we address the issue of the relevance of heterogeneity in the resources distr...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Inferring the Source of Transmission with Phylogenetic Data	journal.pcbi.1003397	null	[ [ "Phylogenetic trees reconstructed from sequences of pathogens contain information on the past transmission dynamics that would be difficult , if not impossible , to obtain through other means .", "Over the past two decades , a number of approaches have been proposed to extract epidemiologically relevant i...	[ "Identifying the source of transmission using pathogen genetic data is complicated by numerous biological , immunological , and behavioral factors .", "A large source of error arises when there is incomplete or sparse sampling of cases .", "Unsampled cases may act as either a common source of infection or as an...	[ "Molecular data from pathogens may be useful for identifying the source of infection and identifying pairs of individuals such that one host transmitted to the other .", "Inference of who acquired infection from whom is confounded by incomplete sampling , and given genetic data only , it is not possible to infer ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cell death", "medicine and health sciences", "cell cycle and cell division", "cell processes", "endocrine physiology", "systems science", "mathematics", "phase diagrams", "growth factors", "waves", "traveling waves", "computer and information sciences", "endocrinology", "chemistry", "dy...	Time scales and wave formation in non-linear spatial public goods games	journal.pcbi.1007361	null	[ [ "Heterogeneity and spatial patterns in population dynamics appear spontaneously in nature , on a wide range of spatial and temporal scales [1 , 2 , 3 , 4] .", "Populations of reproducing individuals are not randomly dispersed , but aggregate according to climate , predatory stress , and resource levels , ...	[ "The co-evolutionary dynamics of competing populations can be strongly affected by frequency-dependent selection and spatial population structure .", "As co-evolving populations grow into a spatial domain , their initial spatial arrangement and their growth rate differences are important factors that determine th...	[ "Evolutionary public good ( PG ) games capture the essence of production of growth-beneficial factors that are vulnerable to exploitation by free-riders who do not carry the cost of production .", "PGs emerge in cellular populations , for example in growing bacteria and cancer cells .", "We study the eco-evolut...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetic mutation", "microbiology", "dna replication", "dna", "bacterial pathogens", "biology", "mutagenesis", "biochemistry", "gram negative", "nucleic acids", "genetics", "dna repair", "genetics and genomics" ]	Unexpected Role for Helicobacter pylori DNA Polymerase I As a Source of Genetic Variability	journal.pgen.1002152	null	[ [ "Phenotypic selection from a pool of genetic variants present in their population allows prokaryotes to successfully adapt to specific niches and changing environments .", "The gram-negative bacterium Helicobacter pylori is one of the most successful human pathogens .", "Indeed , it colonises the stom...	[ "Helicobacter pylori , a human pathogen infecting about half of the world population , is characterised by its large intraspecies variability .", "Its genome plasticity has been invoked as the basis for its high adaptation capacity .", "Consistent with its small genome , H . pylori possesses only two bona fide ...	[ "Helicobacter pylori is the main cause of ulcers and gastric cancers .", "One the characteristics of this bacterial species is that it displays an amazing capacity to change its genetic information .", "This genetic variability provides H . pylori with an adaptation potential that allows it to successfully colo...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "cell biology", "infectious diseases", "eukaryotes" ]	Organizational Changes of the Daughter Basal Complex during the Parasite Replication of Toxoplasma gondii	journal.ppat.0040010	null	[ [ "The phylum Apicomplexa contains ∼5 , 000 species of obligate intracellular protozoan parasites , many of which are important human or animal pathogens .", "Toxoplasma gondii is the most common cause of congenital neurological defects in humans , and an agent for devastating opportunistic infections in im...	[ "The apicomplexans are a large group of parasitic protozoa , many of which are important human and animal pathogens , including Plasmodium falciparum and Toxoplasma gondii .", "These parasites cause disease only when they replicate , and their replication is critically dependent on the proper assembly of the para...	[ "Toxoplasma gondii is one of the most prevalent parasites in warm-blooded animals and a highly important human pathogen .", "It is the most common cause of congenital neurological defects in humans and also causes devastating opportunistic infections in immuno-compromised patients .", "Many of its 5 , 000 relat...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Selection and Spread of Artemisinin-Resistant Alleles in Thailand Prior to the Global Artemisinin Resistance Containment Campaign	journal.ppat.1004789	null	[ [ "Artemisinin combination therapy ( ACT ) has been adopted globally as the first-line treatment for uncomplicated Plasmodium falciparum malaria and has contributed to the reduction in malaria related mortality and morbidity .", "However , resistance to artemisinin poses a threat to the global effort to con...	[ "The recent emergence of artemisinin resistance in the Greater Mekong Subregion poses a major threat to the global effort to control malaria .", "Tracking the spread and evolution of artemisinin-resistant parasites is critical in aiding efforts to contain the spread of resistance .", "A total of 417 patient sam...	[ "The Plasmodium falciparum parasites that cause malaria are evolving resistance to our most effective and potent anti-malarial drugs available , called artemisinins .", "Currently , artemisinin resistance is emerging in a number of countries in the Greater Mekong Subregion , including Cambodia , Thailand , Myanma...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "transfection", "phosphorylation", "rheumatology", "medicine and health sciences", "gene regulation", "enzymes", "biological cultures", "immunology", "enzymology", "ubiquitin ligases", "clinical medicine", "immunoprecipitation", "molecular biology techniques", "ligases", "research and an...	The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response	journal.ppat.1006264	null	[ [ "The innate immune system serves as the first line of host defense against invading microbes .", "Upon recognition by an array of host germline-encoded pattern recognition receptors ( PRRs ) , including Toll-like receptors ( TLRs ) , RIG-I-like receptors ( RLRs ) and DNA sensors , microbial nucleic acids ...	[ "The cyclic GMP-AMP synthase ( cGAS ) , upon cytosolic DNA stimulation , catalyzes the formation of the second messenger 2′3′-cGAMP , which then binds to stimulator of interferon genes ( STING ) and activates downstream signaling .", "It remains to be elucidated how the cGAS enzymatic activity is modulated dynami...	[ "Ubiquitination has been demonstrated to serve as an effective means to catalyze the rapid , dynamic and versatile regulatory processes that are activated when hosts face microbes .", "Given the critical functions of cytosolic DNA sensing pathway in anti-viral innate immune responses and the pathogenesis of autoi...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Structure-Based Alignment and Consensus Secondary Structures for Three HIV-Related RNA Genomes	journal.pcbi.1004230	null	[ [ "RNA plays a direct role in most biological processes [1] , and multiple examples of RNA function are found in the replication cycles of positive-strand RNA lentiviruses [2] .", "Viral RNA genomes function at two distinct levels: in the linear encoding of protein sequences and in functional higher-order R...	[ "HIV and related primate lentiviruses possess single-stranded RNA genomes .", "Multiple regions of these genomes participate in critical steps in the viral replication cycle , and the functions of many RNA elements are dependent on the formation of defined structures .", "The structures of these elements are st...	[ "Human immunodeficiency virus ( HIV ) is a persistent and critical threat to human health .", "Replication and pathogenesis of HIV is governed by information encoded in its single-stranded RNA genome .", "In addition to coding for viral proteins , the HIV genomic RNA forms base paired and higher-order structure...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "body fluids", "immune cells", "pathology and laboratory medicine", "pathogens", "immunology", "tropical diseases", "microbiology", "parasitic diseases", "parasitic protozoans", "parasitology", "retroviruses", "parasitemia", "urine", "immu...	Use of a Chagas Urine Nanoparticle Test (Chunap) to Correlate with Parasitemia Levels in T. cruzi/HIV Co-infected Patients	journal.pntd.0004407	null	[ [ "Chagas disease , caused by the protozoan Trypanosoma cruzi , affects an estimated 7 . 8 million people in the Americas [1] .", "Similar to HIV infection , Chagas disease is most prevalent in the adult population [2] .", "Massive rural-to-urban migration throughout has brought many cases of chronic Ch...	[ "Early diagnosis of reactivated Chagas disease in HIV patients could be lifesaving .", "In Latin America , the diagnosis is made by microscopical detection of the T . cruzi parasite in the blood; a diagnostic test that lacks sensitivity .", "This study evaluates if levels of T . cruzi antigens in urine , determ...	[ "Reactivation of Chagas disease in people living with HIV is a serious clinical condition that is associated with high mortality .", "Hence , early diagnosis and treatment can be lifesaving .", "Although there are not well accepted criteria to identify patients at risk of reactivation , parasitemia levels are u...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/epigenetics", "molecular biology/histone modification", "molecular biology/dna methylation" ]	Antagonism between DNA and H3K27 Methylation at the Imprinted Rasgrf1 Locus	journal.pgen.1000145	null	[ [ "In mammals , imprinted loci are expressed from only one allele .", "Accompanying and controlling monoallelic expression are allele-specific epigenetic modifications influenced by an imprinting control region ( ICR ) .", "Within this region , there is a differentially methylated domain ( DMD ) that is...	[ "At the imprinted Rasgrf1 locus in mouse , a cis-acting sequence controls DNA methylation at a differentially methylated domain ( DMD ) .", "While characterizing epigenetic marks over the DMD , we observed that DNA and H3K27 trimethylation are mutually exclusive , with DNA and H3K27 methylation limited to the pat...	[ "Methylation of DNA and histones exert profound and inherited effects on gene expression .", "These occur without changes to the underlying DNA sequence and are considered epigenetic effects .", "Disrupting epigenetic states can cause developmental abnormalities and cancer .", "Very little is known about how ...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "pneumococcus", "chemical compounds", "phosphates", "enzymes", "pathogens", "enzymology", "microbiology", "staphylococcus aureus", "sodium phosphate", "bacteria", "bacterial pathogens", "proteins", "medical microbiology...	In vitro characterization of the antivirulence target of Gram-positive pathogens, peptidoglycan O-acetyltransferase A (OatA)	journal.ppat.1006667	null	[ [ "Multi-drug resistance amongst important human pathogens , such as methicillin-resistant Staphylococcus aureus ( MRSA ) , vancomycin-resistant Enterococcus ( VRE ) and drug-resistant Streptococcus pneumoniae , continues to challenge clinicians and threaten the lives of infected patients to the extent that the...	[ "The O-acetylation of the essential cell wall polymer peptidoglycan occurs in most Gram-positive bacterial pathogens , including species of Staphylococcus , Streptococcus and Enterococcus .", "This modification to peptidoglycan protects these pathogens from the lytic action of the lysozymes of innate immunity sys...	[ "Multi-drug resistance amongst important human pathogens , such as methicillin-resistant Staphylococcus aureus ( MRSA ) , vancomycin-resistant Enterococcus ( VRE ) and drug-resistant Streptococcus pneumoniae ( DRSP ) , continues to challenge clinicians and threaten the lives of infected patients .", "Of the sever...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "dermatology", "rheumatology", "medicine and health sciences", "pathology and laboratory medicine", "immunology", "microbiology", "bacterial diseases", "rheumatoid arthritis", "skin infections", "emerging infectious diseases", "bacterial pathogens", "veterinary science", "infectious diseases...	Strain-Specific Variation of the Decorin-Binding Adhesin DbpA Influences the Tissue Tropism of the Lyme Disease Spirochete	journal.ppat.1004238	null	[ [ "Lyme disease is distributed worldwide and is the most common arthropod-borne infectious disease in the United States [1]–[3] .", "The causative agent is the spirochete Borrelia burgdorferi sensu lato , which includes B . burgdorferi sensu stricto , B . garinii , and B . afzelii [4] [5] .", "Following...	[ "Lyme disease spirochetes demonstrate strain- and species-specific differences in tissue tropism .", "For example , the three major Lyme disease spirochete species , Borrelia burgdorferi sensu stricto , B . garinii , and B . afzelii , are each most commonly associated with overlapping but distinct spectra of clin...	[ "Lyme disease , the most common vector-borne disease in the United States , is caused by a bacterium , Borrelia burgdorferi .", "This bacterium infects the skin at the site of the tick bite and then can spread to other tissues , such as the heart , joints or nervous system , causing carditis , arthritis or neurol...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "sequencing techniques", "invertebrates", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "viral transmission and infection", "pathogens", "microbiology", "vertebrates", "animals", "mammals", "primates", "viruses", "rna viruses", "molecular biology tec...	Molecularly barcoded Zika virus libraries to probe in vivo evolutionary dynamics	journal.ppat.1006964	null	[ [ "Zika virus ( ZIKV; Flaviviridae , Flavivirus ) infection during pregnancy can cause congenital Zika syndrome ( CZS ) —a collection of neurological , visual , auditory , and developmental birth defects—in at least 5% of babies [1] .", "The frequency of vertical transmission is not known , although data su...	[ "Defining the complex dynamics of Zika virus ( ZIKV ) infection in pregnancy and during transmission between vertebrate hosts and mosquito vectors is critical for a thorough understanding of viral transmission , pathogenesis , immune evasion , and potential reservoir establishment .", "Within-host viral diversity...	[ "Understanding the complex dynamics of Zika virus ( ZIKV ) infection during pregnancy and during transmission to and from vertebrate host and mosquito vector is critical for a thorough understanding of viral transmission , pathogenesis , immune evasion , and reservoir establishment .", "We sought to develop a vir...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "humoral immunity", "medicine", "complement system", "pneumococcus", "immune activation", "immunity to infections", "immunology", "microbiology", "host-pathogen interaction", "animal models", "bacterial diseases", "adaptive immunity", "model organisms", "immune defense", "bacterial patho...	The Lectin Pathway of Complement Activation Is a Critical Component of the Innate Immune Response to Pneumococcal Infection	journal.ppat.1002793	null	[ [ "Streptococcus pneumoniae infection is a major cause of pneumonia , otitis media , septicemia and meningitis [1] , [2] .", "Complement–driven opsonophagocytosis is a prominent feature of the host response to pneumococcal infections , [3] .", "Complement provides protection against invading microorgani...	[ "The complement system plays a key role in host defense against pneumococcal infection .", "Three different pathways , the classical , alternative and lectin pathways , mediate complement activation .", "While there is limited information available on the roles of the classical and the alternative activation pa...	[ "Streptococcus pneumoniae is a major human pathogen that causes pneumonia , septicemia and meningitis .", "The host defense against pneumococci is largely dependent on complement , a system of blood proteins which , when activated , attach to bacteria , targeting them for clearance by phagocytes .", "There are ...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "socioeconomic aspects of health", "public health and epidemiology", "mental health", "behavioral and social aspects of health", "global health", "anxiety disorders", "public health", "psychiatry" ]	Delayed Psychological Morbidity Associated with Snakebite Envenoming	journal.pntd.0001255	null	[ [ "Snakebite is a significant health issue in the rural tropics .", "Globally , it has been estimated that at least 421 , 000 envenomings and 20 , 000 deaths occur due to snakebite each year each year , and that these numbers may even be as high as 1 . 8 million envenoming and 94 000 deaths [1] .", "The...	[ "The psychological impact of snakebite on its victims , especially possible late effects , has not been systematically studied .", "To assess delayed somatic symptoms , depressive disorder , post-traumatic stress disorder ( PTSD ) , and impairment in functioning , among snakebite victims .", "The study had qual...	[ "Snakebite envenoming is a neglected public health problem , especially in rural areas of tropical and sub-tropical countries .", "Little is known about the long term effects , and even less about the possible psychological effects , of snakebites and envenoming .", "We investigated the possible psychological i...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chemical bonding", "chemical characterization", "chromosome structure and function", "anaphase", "cell cycle and cell division", "cell processes", "dna-binding proteins", "nucleotides", "telomeres", "dna replication", "dna", "physical chemistry", "research and analysis methods", "dna bind...	STN1 OB Fold Mutation Alters DNA Binding and Affects Selective Aspects of CST Function	journal.pgen.1006342	null	[ [ "Although DNA replication must occur rapidly and with high fidelity , the replisome frequently encounters obstacles such as DNA damage or repetitive sequence that cause the replication fork to stall .", "Since stalled forks can lead to double strand breaks and genomic instability , multiple pathways exist...	[ "Mammalian CST ( CTC1-STN1-TEN1 ) participates in multiple aspects of telomere replication and genome-wide recovery from replication stress .", "CST resembles Replication Protein A ( RPA ) in that it binds ssDNA and STN1 and TEN1 are structurally similar to RPA2 and RPA3 .", "Conservation between CTC1 and RPA1 ...	[ "Mammalian CST ( CTC1/STN1/TEN1 ) is a three protein complex that aids in several steps during telomere replication and has genome-wide roles during recovery from replication fork stalling .", "Loss of CST leads to abnormalities in telomere structure , genomic instability and defects in chromosome segregation .",...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/immunodeficiency viruses", "virology/host invasion and cell entry" ]	Early Steps of HIV-1 Fusion Define the Sensitivity to Inhibitory Peptides That Block 6-Helix Bundle Formation	journal.ppat.1000585	null	[ [ "HIV Env-induced fusion between the viral and cellular membrane progresses through a series of steps that begin with binding of the gp120 subunit to CD4 .", "This step results in the formation of the gp120 bridging sheet which , along with the third hypervariable loop ( V3 loop ) , forms the coreceptor bi...	[ "The HIV envelope ( Env ) glycoprotein mediates membrane fusion through sequential interactions with CD4 and coreceptors , followed by the refolding of the transmembrane gp41 subunit into the stable 6-helix bundle ( 6HB ) conformation .", "Synthetic peptides derived from the gp41 C-terminal heptad repeat domain (...	[ "The human immunodeficiency virus ( HIV ) envelope glycoprotein ( Env ) mediates fusion between the viral and cell membranes .", "The fusion is initiated by Env-receptor interactions and is followed by coreceptor binding and refolding of the transmembrane gp41 subunit .", "The gp41 refolding proceeds through se...	2009
[ "Introduction", "Methods", "Results", "Discussion", "Conclusions and recommendations" ]	[ "medicine and health sciences", "ecology and environmental sciences", "leptospira", "pathology and laboratory medicine", "pathogens", "population dynamics", "tropical diseases", "microbiology", "vertebrates", "animals", "mammals", "animal models", "bacterial diseases", "review", "model o...	Leptospira infection in rats: A literature review of global prevalence and distribution	journal.pntd.0007499	null	[ [ "Leptospirosis is a major zoonotic disease worldwide , having significant impact on both human and animal health [1 , 2] .", "It is known to be the most widespread zoonosis in the world [3] , affecting an estimated 1 . 03 million people and causing 58 , 900 deaths annually [4] .", "Leptospirosis can a...	[ "The role of rodents in Leptospira epidemiology and transmission is well known worldwide .", "Rats are known to carry different pathogenic serovars of Leptospira spp .", "capable of causing disease in humans and animals .", "Wild rats ( Rattus spp . ) , especially the Norway/brown rat ( Rattus norvegicus ) an...	[ "The role of rodents in the transmission of many diseases , including leptospirosis , is widely known .", "Rats abundant in urban and peridomestic environments are the most important reservoirs and sources of Leptospira infection in humans and animals .", "Leptospirosis is a significant but neglected disease of...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	An Emerging Allee Effect Is Critical for Tumor Initiation and Persistence	journal.pcbi.1004366	null	[ [ "Tumor cells possess a remarkable phenotypic plasticity that allows for adaptation to changing microenvironmental conditions [1 , 2] .", "Well-known examples are the epithelial-mesenchymal transition [3 , 4] and the shift from ATP generation through oxidative phosphorylation to an anaerobic , glycolytic m...	[ "Tumor cells develop different strategies to cope with changing microenvironmental conditions .", "A prominent example is the adaptive phenotypic switching between cell migration and proliferation .", "While it has been shown that the migration-proliferation plasticity influences tumor spread , it remains uncle...	[ "Controlling tumor growth remains a major medical challenge .", "Current clinical therapies focus on strategies to reduce tumor cell proliferation .", "However , during tumor progression , tumor cells may switch between proliferative and migratory behaviors , thereby allowing adaptation to microenvironmental ch...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "public health and epidemiology/epidemiology", "infectious diseases/helminth infections", "public health and epidemiology/infectious diseases", "infectious diseases/epidemiology and control of infectious diseases", "genetics and genomics/population geneti...	Population Genetics of Schistosoma japonicum within the Philippines Suggest High Levels of Transmission between Humans and Dogs	journal.pntd.0000340	null	[ [ "Infection by the Asian blood fluke Schistosoma japonicum remains an important public health burden in the Philippines , China and parts of Indonesia , despite continued efforts of ongoing control programs [1] .", "In the Philippines alone , it has been estimated that approximately 6 . 7 million people li...	[ "Schistosoma japonicum , which remains a major public health problem in the Philippines and mainland China , is the only schistosome species for which zoonotic transmission is considered important .", "While bovines are suspected as the main zoonotic reservoir in parts of China , the relative contributions of var...	[ "Schistosomiasis is a disease caused by parasitic worms known as schistosomes , which infect about 200 million people worldwide .", "In the Philippines , as in China , the species of schistosome ( Schistosoma japonicum ) which causes the disease infects not only humans , but also many other species of mammals .",...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "parasite groups", "plasmodium", "chromosome structure and function", "enzymes", "enzymology", "cloning", "parasitic protozoans", "parasitology", "dna transcription", "telomeres", "apicomplexa", "protozoans", "dna replication", "dna", "molecular biology techniques", "research and analy...	RecQ helicases in the malaria parasite Plasmodium falciparum affect genome stability, gene expression patterns and DNA replication dynamics	journal.pgen.1007490	null	[ [ "Protozoan Plasmodium parasites are the causative agents of human malaria , a disease responsible for widespread morbidity and almost half a million deaths each year [1] .", "Most malaria deaths are caused by the species P . falciparum , although four other Plasmodium species also infect humans .", "P...	[ "The malaria parasite Plasmodium falciparum has evolved an unusual genome structure .", "The majority of the genome is relatively stable , with mutation rates similar to most eukaryotic species .", "However , some regions are very unstable with high recombination rates , driving the generation of new immune eva...	[ "Human malaria is caused by Plasmodium parasites , with most of the mortality ( almost half a million deaths each year ) being caused by one species , Plasmodium falciparum .", "This parasite has an unusual genome: it is exceptionally biased towards A and T nucleotides rather than G and C , and it contains specif...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/reproductive immunology", "microbiology/immunity to infections", "respiratory medicine/respiratory infections", "microbiology/innate immunity", "immunology/immunity to infections", "immunology/innate immunity", "respiratory medicine/asthma", "microbiology/cellular microbiology and pathogen...	Interleukin-13 Promotes Susceptibility to Chlamydial Infection of the Respiratory and Genital Tracts	journal.ppat.1001339	null	[ [ "Chlamydiae are Gram-negative , obligate intracellular bacteria that commonly cause respiratory and genital tract as well as ocular infections in humans .", "Globally , Chlamydophila pneumoniae has been estimated to account for 5% of cases of bronchitis and sinusitis , and up to 22% of cases of community-...	[ "Chlamydiae are intracellular bacteria that commonly cause infections of the respiratory and genital tracts , which are major clinical problems .", "Infections are also linked to the aetiology of diseases such as asthma , emphysema and heart disease .", "The clinical management of infection is problematic and a...	[ "Chlamydial infections are a common cause of respiratory , genital tract and eye diseases , and infections are clinically associated with the aetiology of asthma , emphysema , heart disease and Alzheimer's .", "However , it is not known what immune factors regulate enhanced susceptibility to infection and immunop...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "marine and aquatic sciences/evolutionary biology", "biophysics/theory and simulation", "computational biology/computational neuroscience", "physiology", "evolutionary biology", "computational biology/systems biology" ]	Mammalian Sleep Dynamics: How Diverse Features Arise from a Common Physiological Framework	journal.pcbi.1000826	null	[ [ "The diversity of mammalian sleep poses a great challenge to those studying the nature and function of sleep .", "Typical daily sleep durations range from 3 h in horses to 19 h in bats [1] , [2] , which has led to recent speculation that sleep has no universal function beyond timing environmental interact...	[ "Mammalian sleep varies widely , ranging from frequent napping in rodents to consolidated blocks in primates and unihemispheric sleep in cetaceans .", "In humans , rats , mice and cats , sleep patterns are orchestrated by homeostatic and circadian drives to the sleep–wake switch , but it is not known whether this...	[ "The field of sleep physiology has made huge strides in recent years , uncovering the neurological structures which are critical to sleep regulation .", "However , given the small number of species studied in such detail in the laboratory , it remains to be seen how universal these mechanisms are across the whole...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "genome expression analysis", "rna interference", "gene regulation", "genome analysis tools", "molecular genetics", "sequence analysis", "gene expression", "biology", "rna processing", "genetics", "genomics", "computational biology", "genetics and genomic...	Single Nucleotide Polymorphisms Can Create Alternative Polyadenylation Signals and Affect Gene Expression through Loss of MicroRNA-Regulation	journal.pcbi.1002621	null	[ [ "In protein-coding genes , the polyadenylation process consists of cleaving the end of the 3′ untranslated region ( UTR ) of precursor messenger RNA ( pre-mRNA ) and adding a polyadenylation ( polyA ) tail .", "Alternative polyadenylation ( APA ) can occur when several polyadenylation ( polyA ) signals li...	[ "Alternative polyadenylation ( APA ) can for example occur when a protein-coding gene has several polyadenylation ( polyA ) signals in its last exon , resulting in messenger RNAs ( mRNAs ) with different 3′ untranslated region ( UTR ) lengths .", "Different 3′UTR lengths can give different microRNA ( miRNA ) regu...	[ "Variants in DNA that affect gene expression—so-called regulatory variants—are thought to play important roles in common complex diseases , such as cancer .", "In contrast to variants in protein-coding regions , regulatory variants do not affect protein sequence and function .", "Instead , regulatory variants a...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "nutrition", "diabetes and endocrinology", "mus (mouse)", "molecular biology" ]	PPAR gamma 2 Prevents Lipotoxicity by Controlling Adipose Tissue Expandability and Peripheral Lipid Metabolism	journal.pgen.0030064	null	[ [ "An adipocentric view of the Metabolic Syndrome ( MS ) considers obesity as the major factor leading to insulin resistance in peripheral metabolic tissues .", "However , the link between obesity and insulin resistance is complex , as indicated by the fact that some extremely obese people are glucose toler...	[ "Peroxisome proliferator activated receptor gamma 2 ( PPARg2 ) is the nutritionally regulated isoform of PPARg .", "Ablation of PPARg2 in the ob/ob background , PPARg2−/− Lepob/Lepob ( POKO mouse ) , resulted in decreased fat mass , severe insulin resistance , β-cell failure , and dyslipidaemia .", "Our results...	[ "It is known that obesity is linked to type 2 diabetes , however how obesity causes insulin resistance and diabetes is not well understood .", "Some extremely obese people are not diabetic , while other less obese people develop severe insulin resistance and diabetes .", "We believe diabetes occurs when adipose...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology", "evolutionary biology", "genetics and genomics" ]	Hotspots of Biased Nucleotide Substitutions in Human Genes	journal.pbio.1000026	Natural selection is commonly believed to be the main engine of functional genetic change, but a separate neutral evolutionary process linked to recombination may have contributed significantly to the divergence of human proteins.	[ [ "Whole-genome comparisons have revealed hundreds of noncoding elements that are extremely conserved across mammals but show evidence for accelerated evolution along the human lineage [1–4] .", "One possible explanation for these human-accelerated regions ( HARs ) is the action of positive selection in the...	[ "Genes that have experienced accelerated evolutionary rates on the human lineage during recent evolution are candidates for involvement in human-specific adaptations .", "To determine the forces that cause increased evolutionary rates in certain genes , we analyzed alignments of 10 , 238 human genes to their orth...	[ "Regions of the human genome that appear to evolve rapidly may have been under strong positive selection and could contain the genetic changes responsible for the uniqueness of our species .", "However , neutral ( nonadaptive ) evolutionary processes can give rise to signals that can be mistaken as signs of selec...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Targeted Ablation of Crb1 and Crb2 in Retinal Progenitor Cells Mimics Leber Congenital Amaurosis	journal.pgen.1003976	null	[ [ "During vertebrate retina development , one type of glial cell and six types of neurons are formed by the orderly generation of post-mitotic cells from a common pool of retinal progenitor cells [1] , [2] .", "In this temporally fine-tuned process , ganglion cells are generated first , followed by horizont...	[ "Development in the central nervous system is highly dependent on the regulation of the switch from progenitor cell proliferation to differentiation , but the molecular and cellular events controlling this process remain poorly understood .", "Here , we report that ablation of Crb1 and Crb2 genes results in sever...	[ "Mutations in the human CRB1 gene lead to one of the most severe forms of retinal dystrophies , called Leber congenital amaurosis .", "Here , we report that ablation of CRB1 and the second family member CRB2 are crucial for proper retinal development .", "These mice display severe impairment of retinal function...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "skin", "invertebrates", "medicine and health sciences", "rna interference", "integumentary system", "caenorhabditis", "gene regulation", "regulatory proteins", "dna-binding proteins", "animals", "animal models", "caenorhabditis elegans", "model organisms", "immunoprecipitation", "experi...	Evolutionary plasticity in the innate immune function of Akirin	journal.pgen.1007494	null	[ [ "A fundamental part of innate immune responses is the regulated expression of defence genes .", "In both vertebrates and many invertebrates , including Drosophila , two of the key regulators controlling innate immunity are the Rel-homology domain ( RHD ) protein NF-κB and its protein partner IκB [1] .", ...	[ "Eukaryotic gene expression requires the coordinated action of transcription factors , chromatin remodelling complexes and RNA polymerase .", "The conserved nuclear protein Akirin plays a central role in immune gene expression in insects and mammals , linking the SWI/SNF chromatin-remodelling complex with the tra...	[ "When animals are infected , as part of their innate immune response , they switch on defence genes that encode proteins that help fight pathogens .", "We use the nematode Caenorhabditis elegans to understand the steps in this process .", "When infected , C . elegans can turn on clusters of antimicrobial peptid...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biophysics/theory and simulation", "biophysics/biomacromolecule-ligand interactions", "biochemistry/biomacromolecule-ligand interactions", "biochemistry/theory and simulation", "biophysics/membrane proteins and energy transduction", "computational biology/molecular dynamics", "biochemistry/membrane pro...	Predicting Novel Binding Modes of Agonists to β Adrenergic Receptors Using All-Atom Molecular Dynamics Simulations	journal.pcbi.1001053	null	[ [ "Beta adrenergic receptors are a class of transmembrane receptors responsible for binding catecholamines , such as the endogenous hormone adrenaline or the neurotransmitter noradrenaline .", "They belong to the G-protein-coupled receptors ( GPCRs ) family and are crucially involved in heart muscle contrac...	[ "Understanding the binding mode of agonists to adrenergic receptors is crucial to enabling improved rational design of new therapeutic agents .", "However , so far the high conformational flexibility of G protein-coupled receptors has been an obstacle to obtaining structural information on agonist binding at atom...	[ "G-protein coupled receptors are the largest family of membrane proteins in the human genome and they constitute the largest class of drug targets .", "Amongst them , beta adrenergic receptors are involved in the regulation of muscular and vascular tone and are thus molecular targets for the treatment of various ...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "medicine and health sciences", "methods and resources", "ustilago maydis", "pathology and laboratory medicine", "fungal genetics", "pathogens", "population genetics", "gene pool", "fungi", "plant science", "model organisms", "experimental organism systems", "genome analys...	In vivo insertion pool sequencing identifies virulence factors in a complex fungal–host interaction	journal.pbio.2005129	null	[ [ "Virulence factors are key for successful infections by pathogens .", "Their identification is of major interest because of the necessity to develop effective counter strategies .", "For instance , fungal virulence factors are typically identified by mutating single loci in fungi , followed by individ...	[ "Large-scale insertional mutagenesis screens can be powerful genome-wide tools if they are streamlined with efficient downstream analysis , which is a serious bottleneck in complex biological systems .", "A major impediment to the success of next-generation sequencing ( NGS ) -based screens for virulence factors ...	[ "Insertion mutant screens are widely used to identify genotype–phenotype relationships .", "In negative selection screens , a major limitation is the efficient identification of mutants that are lost or retained after selection .", "To identify these mutants , the two genomic sequences flanking the insertion ca...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "genetics and genomics/population genetics", "public health and epidemiology/infectious diseases", "evolutionary biology/evolutionary ecology" ]	High Levels of Genetic Differentiation between Ugandan Glossina fuscipes fuscipes Populations Separated by Lake Kyoga	journal.pntd.0000242	null	[ [ "Tsetse ( Diptera: Glossinidae ) are the sole vectors of pathogenic trypanosomes in tropical Africa , where they cause Human African trypanosomiasis ( HAT ) , or sleeping sickness .", "HAT is a zoonosis caused by the flagellated protozoa Trypanosoma brucei rhodesiense in East and Southern Africa and by T ...	[ "Glossina fuscipes fuscipes is the major vector of human African trypanosomiasis , commonly referred to as sleeping sickness , in Uganda .", "In western and eastern Africa , the disease has distinct clinical manifestations and is caused by two different parasites: Trypanosoma brucei rhodesiense and T . b .", "g...	[ "The two types of sleeping sickness in West and East Africa are markedly distinct , require different treatments , and are caused by different parasites .", "The only country where both parasites are present is Uganda , where they are separated by a narrow 160 km disease-free belt .", "Because there is no restr...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "microbial metabolism", "emerging infectious diseases", "vector biology", "biology", "microbiology", "ticks", "host-pathogen interaction", "bacterial biochemistry", "bacterial pathogens", "microbial growth and development", "pathogenesis" ]	Borrelia burgdorferi Requires Glycerol for Maximum Fitness During The Tick Phase of the Enzootic Cycle	journal.ppat.1002102	null	[ [ "Borrelia burgdorferi is the spirochetal agent of Lyme disease , the most frequently reported vector-borne disease in the United States [1] .", "In the Northeastern United States , B . burgdorferi is transmitted between mammalian hosts by the bite of the black legged deer tick , Ixodes scapularis , with t...	[ "Borrelia burgdorferi , the spirochetal agent of Lyme disease , is a vector-borne pathogen that cycles between a mammalian host and tick vector .", "This complex life cycle requires that the spirochete modulate its gene expression program to facilitate growth and maintenance in these diverse milieus .", "B . bu...	[ "Borrelia burgdorferi is the vector-borne pathogen that causes Lyme disease .", "It has a complex life cycle that involves growth in a tick vector and a mammalian host — two diverse environments that present B . burgdorferi with alternative carbohydrate sources for support of growth .", "Previous studies sugges...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "virology/virion structure, assembly, and egress", "virology/viral replication and gene regulation", "virology" ]	Direct Interaction between Two Viral Proteins, the Nonstructural Protein 2CATPase and the Capsid Protein VP3, Is Required for Enterovirus Morphogenesis	journal.ppat.1001066	null	[ [ "Morphogenesis is a crucial step at the end of the virus' life cycle that provides newly synthesized genomes with a protective shell to survive in the extracellular environment yet assures attachment to and penetration into subsequent host cells .", "Morphogenesis of viral genomes must be specific because...	[ "In spite of decades-long studies , the mechanism of morphogenesis of plus-stranded RNA viruses belonging to the genus Enterovirus of Picornaviridae , including poliovirus ( PV ) , is not understood .", "Numerous attempts to identify an RNA encapsidation signal have failed .", "Genetic studies , however , have ...	[ "Enteroviruses are single , plus-stranded RNA viruses that contain a large number of closely related pathogens .", "Human enteroviruses cause altogether >3 billion human infections per year , inflicting diseases ranging from benign ( common cold ) to very serious ( poliomyelitis ) .", "Enterovirus replication h...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	A High-Resolution Whole-Genome Map of Key Chromatin Modifications in the Adult Drosophila melanogaster	journal.pgen.1002380	null	[ [ "Epigenetics refers to the regulation of gene expression that is heritable to daughter cells without alteration of genetic information [1] .", "Epigenetic regulation is commonly achieved via DNA methylation , covalent modification of histones , and association/dissociation of chromatin factors [2] .", ...	[ "Epigenetic research has been focused on cell-type-specific regulation; less is known about common features of epigenetic programming shared by diverse cell types within an organism .", "Here , we report a modified method for chromatin immunoprecipitation and deep sequencing ( ChIP–Seq ) and its use to construct ...	[ "Just as a genome sequence map is indispensible to genetic studies , an epigenome map is crucial for epigenetic research .", "This is especially true for a sophisticated genetic model such as Drosophila melanogaster , where the wealth of information on genetics and developmental biology awaits systematic epigenet...	2011
[ "Introduction", "Results", "Discussion", "Methods", "Statistics" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "granulomas", "immunology", "tropical diseases", "animal models", "bacterial diseases", "model organisms", "signs and symptoms", "materials science", "experimental organism systems", "bacter...	Transmission phenotype of Mycobacterium tuberculosis strains is mechanistically linked to induction of distinct pulmonary pathology	journal.ppat.1007613	null	[ [ "Mtb is one of the most successful pathogens known; yet mechanisms underlying variability in transmission remain poorly understood .", "Pioneering work from Riley and colleagues [1] using TST conversion in guinea pigs that were exposed to air from a TB ward as a measure of infectiousness , found significa...	[ "In a study of household contacts ( HHC ) , households were categorized into High ( HT ) and Low ( LT ) transmission groups based on the proportion of HHC with a positive tuberculin skin test .", "The Mycobacterium tuberculosis ( Mtb ) strains from HT and LT index cases of the households were designated Mtb-HT an...	[ "Mycobacterium tuberculosis ( Mtb ) , the bacteria that causes tuberculosis ( TB ) , is spread through the air from infected patients to their close contacts .", "In a household contact ( HHC ) study of patients with TB , we found that in some households a larger proportion of contacts were infected with Mtb comp...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "medicine", "ophthalmology", "genetics", "biology", "genetics of disease", "genetics and genomics" ]	Genetic Variants on Chromosome 1q41 Influence Ocular Axial Length and High Myopia	journal.pgen.1002753	null	[ [ "Myopia increases the risk of visual morbidity and poses a considerable public health and economic burden globally , especially in Asia , where the prevalence is significantly higher than other parts of the world [1] .", "Human myopia primarily results from an abnormal increase in ocular axial length ( AL...	[ "As one of the leading causes of visual impairment and blindness , myopia poses a significant public health burden in Asia .", "The primary determinant of myopia is an elongated ocular axial length ( AL ) .", "Here we report a meta-analysis of three genome-wide association studies on AL conducted in 1 , 860 Chi...	[ "Myopic individuals exhibit an increase in ocular axial length ( AL ) .", "As a highly heritable ocular biometry of refractive error , identification of quantitative trait loci influencing AL variation would be valuable in informing the biological etiology of myopia .", "We have determined that a genetic locus ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "genetics and genomics/comparative genomics", "evolutionary biology/evolutionary and comparative genetics", "genetics and genomics/epigenetics", "genetics and genomics/medical genetics" ]	The Evolution of Epigenetic Regulators CTCF and BORIS/CTCFL in Amniotes	journal.pgen.1000169	null	[ [ "CCCTC-binding factor ( CTCF ) is a ubiquitously expressed protein that binds to more than 20 , 000 sites within the human genome [1]–[3] .", "The distribution of these binding sites , along with experimental data from several well-characterised loci ( reviewed [4] ) indicates that CTCF acts as an insulat...	[ "CTCF is an essential , ubiquitously expressed DNA-binding protein responsible for insulator function , nuclear architecture , and transcriptional control within vertebrates .", "The gene CTCF was proposed to have duplicated in early mammals , giving rise to a paralogue called “brother of regulator of imprinted s...	[ "Epigenetic mechanisms heritably change gene expression without altering DNA sequence .", "Currently , little is known about the evolution of epigenetic traits , and the genes that control them .", "CTCF is an essential epigenetic regulator that is expressed widely in the tissues of vertebrates and modifies the...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "livestock", "medicine and health sciences", "immunology", "tropical diseases", "geographical locations", "social sciences", "peru", "preventive medicine", "rabies", "farms", "neglected tropical diseases", "vaccination and immunization", "veterinary science", "public and occupational healt...	Quantifying the burden of vampire bat rabies in Peruvian livestock	journal.pntd.0006105	null	[ [ "Knowledge of the number of cases and associated economic losses from infectious diseases ( “disease burden” ) is crucial to allocate resources for prevention and control appropriately .", "Estimating disease burden is a priority for the control of neglected zoonoses [1] but is challenging , particularly ...	[ "Knowledge of infectious disease burden is necessary to appropriately allocate resources for prevention and control .", "In Latin America , rabies is among the most important zoonoses for human health and agriculture , but the burden of disease attributed to its main reservoir , the common vampire bat ( Desmodus ...	[ "The number of cases and monetary cost of a disease guides how resources for prevention and control are allocated .", "In Latin America , rabies transmitted by vampire bats is one of the most recognized zoonoses affecting humans and livestock , but its burden on lives and livelihoods has been difficult to calcula...	2017
[ "Introduction", "Results", "Discussion", "Matherials and methods" ]	[ "plant anatomy", "stem anatomy", "medicine and health sciences", "internodes", "nervous system", "brain", "neuroscience", "macroglial cells", "hormones", "plant science", "testosterone", "nerve fibers", "research and analysis methods", "androgens", "specimen preparation and treatment", ...	Long-lasting masculinizing effects of postnatal androgens on myelin governed by the brain androgen receptor	journal.pgen.1007049	null	[ [ "The incidence and clinical course of many neurological disorders differ between sexes , and elucidating the underlying biological basis has become a high priority challenge [1 , 2] .", "The potential impact of sex differences in brain structure has long been neglected .", "They were indeed believed t...	[ "The oligodendrocyte density is greater and myelin sheaths are thicker in the adult male mouse brain when compared with females .", "Here , we show that these sex differences emerge during the first 10 postnatal days , precisely at a stage when a late wave of oligodendrocyte progenitor cells arises and starts dif...	[ "Sex differences in brain structure are of great scientific and medical interest because the incidence and progress of many neurological and psychiatric disorders differ between males and females .", "They affect neural networks and also the myelin sheaths that insulate and protect axons and thus allow the rapid ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "genome-wide association studies", "microbial metabolism", "enzymes", "host-pathogen interaction", "microbiology", "enzyme metabolism", "staphylococci", "microbial growth and development", "bacterial pathogens", "microbial physiology", "medical microbiology", "metabolic pathw...	Nutrient Limitation Governs Staphylococcus aureus Metabolism and Niche Adaptation in the Human Nose	journal.ppat.1003862	null	[ [ "Staphylococcus aureus is a major cause of human invasive infections ranging from superficial skin and soft tissue infections to severe disseminated diseases such as sepsis and endocarditis [1] .", "S . aureus is also a human commensal and part of the microbiota in healthy individuals , which facilitates ...	[ "Colonization of the human nose by Staphylococcus aureus in one-third of the population represents a major risk factor for invasive infections .", "The basis for adaptation of S . aureus to this specific habitat and reasons for the human predisposition to become colonized have remained largely unknown .", "Huma...	[ "Many severe bacterial infections are caused by endogenous pathogens colonizing human body surfaces .", "Eradication of notorious pathogens such as Staphylococcus aureus from risk patients has become an important preventive strategy .", "However , efficient decolonization agents are rare , and the living condit...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology/social and behavioral determinants of health", "infectious diseases/gastrointestinal infections", "infectious diseases/epidemiology and control of infectious diseases" ]	Informal Urban Settlements and Cholera Risk in Dar es Salaam, Tanzania	journal.pntd.0000631	null	[ [ "In 2008 , for the first time in human history , more than half of the world's population was living in urban areas , and this proportion is expected to increase .", "Much of the future growth in urban areas is expected to take place in developing countries , with Africa and Asia predicted to have nearly ...	[ "As a result of poor economic opportunities and an increasing shortage of affordable housing , much of the spatial growth in many of the world's fastest-growing cities is a result of the expansion of informal settlements where residents live without security of tenure and with limited access to basic infrastructure...	[ "In 2008 , for the first time in human history , more than half of the world's population was living in urban areas , and this proportion is expected to increase .", "As a result of poor economic opportunities and an increasing shortage of affordable housing , much of the spatial growth in many of the world's fas...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Feature Selection Methods for Identifying Genetic Determinants of Host Species in RNA Viruses	journal.pcbi.1003254	null	[ [ "Emerging infectious diseases ( EIDs ) continue to represent a significant public health threat , as illustrated by the 2009 H1N1 influenza pandemic and the 2003 severe acute respiratory syndrome ( SARS ) epidemic .", "Of particular concern are the 60%+ of EIDs of zoonotic origin [1] , [2] .", "In add...	[ "Despite environmental , social and ecological dependencies , emergence of zoonotic viruses in human populations is clearly also affected by genetic factors which determine cross-species transmission potential .", "RNA viruses pose an interesting case study given their mutation rates are orders of magnitude highe...	[ "Moving away from genome scan methods used for human GWAS ( ultimately inappropriate for the short highly polymorphic genomes of RNA viruses ) , our work shows the power and potential of multi-class machine learning algorithms in inferring the functional genetic changes associated with phenotypic change ( e . g . c...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Leukocyte-Derived IFN-α/β and Epithelial IFN-λ Constitute a Compartmentalized Mucosal Defense System that Restricts Enteric Virus Infections	journal.ppat.1004782	null	[ [ "The intestine has to maintain tolerance to the symbiotic gastrointestinal microflora , while mounting an effective immune response when challenged with opportunistic bacteria or enteric viruses .", "Thus , the intestinal mucosa , composed of the lining epithelium and underlying lamina propria cells , for...	[ "Epithelial cells are a major port of entry for many viruses , but the molecular networks which protect barrier surfaces against viral infections are incompletely understood .", "Viral infections induce simultaneous production of type I ( IFN-α/β ) and type III ( IFN-λ ) interferons .", "All nucleated cells are...	[ "Virus-induced interferon consists of two distinct families of molecules , IFN-α/β and IFN-λ .", "IFN-α/β family members are key antiviral molecules that confer protection against a large number of viruses infecting a wide variety of cell types .", "By contrast , IFN-λ responses are largely confined to epitheli...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Conclusions" ]	[ "medicine", "preventive medicine", "infectious diseases", "rabies", "veterinary diseases", "public health and epidemiology", "veterinary epidemiology", "global health", "zoonotic diseases", "public health", "veterinary science" ]	Dog Bite Histories and Response to Incidents in Canine Rabies-Enzootic KwaZulu-Natal, South Africa	journal.pntd.0002059	null	[ [ "Rabies kills tens of thousands of people in developing countries each year , and it is estimated that almost half of global rabies incidences occur in Africa [1]–[2] .", "However , one major factor compounding the problems of rabies is a high probability of disease underreporting .", "Studies in Tanz...	[ "The objective of this paper is to report evaluated observations from survey records captured through a cross-sectional observational study regarding canine populations and dog owners in rabies enzootic KwaZulu-Natal province , South Africa .", "Our aim was to evaluate respondent knowledge of canine rabies and re...	[ "Canine rabies has been enzootic to KwaZulu-Natal province , South Africa since the mid-1970's .", "Vaccination requirements for domestic species and animal control laws enforced in industrialized countries frequently eliminate the need for rabies post exposure prophylaxis ( PEP ) when an animal bite occurs .", ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/medical microbiology", "microbiology/innate immunity" ]	The Antimicrobial Peptide Histatin-5 Causes a Spatially Restricted Disruption on the Candida albicans Surface, Allowing Rapid Entry of the Peptide into the Cytoplasm	journal.ppat.1000190	null	[ [ "Oral candidiasis is most commonly associated with individuals infected with the human immunodeficiency virus ( HIV ) , and it is also seen in infants , patients with diabetes mellitus , and those receiving broad-spectrum antibiotics .", "However , oral candidiasis is relatively uncommon in the general po...	[ "Antimicrobial peptides play an important role in host defense against microbial pathogens .", "Their high cationic charge and strong amphipathic structure allow them to bind to the anionic microbial cell membrane and disrupt the membrane bilayer by forming pores or channels .", "In contrast to the classical po...	[ "In most healthy individuals , the yeast Candida albicans is found within the oral cavity as part of the normal microflora .", "Though under immunocompromising conditions , this benign microbe can become an opportunistic pathogen causing oral candidiasis ( i . e . thrush ) .", "Although antifungal drugs are typ...	2008
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "drosophila", "genetics and genomics", "developmental biology" ]	Sustained Post-Mating Response in Drosophila melanogaster Requires Multiple Seminal Fluid Proteins	journal.pgen.0030238	null	[ [ "Molecules in seminal fluid induce physiological changes in females , thereby affecting the reproductive capacity of both sexes ( [1–6]; for reviews see [7–9] ) .", "In some animals , the absence or different levels of certain individual seminal proteins can lead to sterility ( e . g . , [10 , 11] ) .", ...	[ "Successful reproduction is critical to pass genes to the next generation .", "Seminal proteins contribute to important reproductive processes that lead to fertilization in species ranging from insects to mammals .", "In Drosophila , the male's accessory gland is a source of seminal fluid proteins that affect t...	[ "In sexually reproducing organisms , sperm enter the female in combination with seminal proteins that are critical for fertility .", "These proteins can activate sperm or enhance sperm storage within the female , and can improve the chance that sperm will fertilize eggs .", "Understanding the action of seminal ...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "auditory system", "cognitive neuroscience", "computational neuroscience", "psychophysics", "biology and life sciences", "psychoacoustics", "sensory perception", "computational biology", "sensory systems", "neuroscience" ]	Characterizing the Impact of Category Uncertainty on Human Auditory Categorization Behavior	journal.pcbi.1003715	null	[ [ "Categorization is a natural and adaptive process that allows the brain to organize the typically high-dimensional and continuous sensory information into robust hierarchical and discrete representations .", "These discrete representations , or categories , are a means to mentally manipulate , reason abou...	[ "Categorization is an important cognitive process .", "However , the correct categorization of a stimulus is often challenging because categories can have overlapping boundaries .", "Whereas perceptual categorization has been extensively studied in vision , the analogous phenomenon in audition has yet to be sys...	[ "Categorization is an important cognitive process that allows us to simplify , extract meaning from , and respond to objects in the sensory environment .", "However , categorization is complicated because an object can belong to multiple categories .", "Thus , to inform our categorical judgments , we must make ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "model organisms", "genetics", "biology", "microbiology", "molecular cell biology" ]	Final Pre-40S Maturation Depends on the Functional Integrity of the 60S Subunit Ribosomal Protein L3	journal.pgen.1004205	null	[ [ "Ribosomes are very intricate ribonucleoprotein particles that catalyse protein synthesis .", "In all organisms , ribosomes are composed of two ribosomal subunits ( r-subunits ) , the large one ( 60S , LSU ) being about twice the size of the small one ( 40S , SSU ) [1] , [2] .", "In eukaryotes , synth...	[ "Ribosomal protein L3 is an evolutionarily conserved protein that participates in the assembly of early pre-60S particles .", "We report that the rpl3[W255C] allele , which affects the affinity and function of translation elongation factors , impairs cytoplasmic maturation of 20S pre-rRNA .", "This was not seen...	[ "Recent progress has provided us with detailed knowledge of the structure and function of eukaryotic ribosomes .", "However , our understanding of the intricate processes of pre-ribosome assembly and the transition to translation-competent ribosomal subunits remains incomplete .", "The early and intermediate st...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "chemical compounds", "pathogens", "metabolic processes", "microbiology", "pseudomonas aeruginosa", "fermentation", "opportunistic pathogens", "bacteria", "bacterial pathogens", "pseudomonas", "propionates"...	Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease	journal.ppat.1005846	null	[ [ "Mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator ( CFTR ) protein cause an imbalance of ion transport that leads to mucus hyperviscosity and impaired mucociliary clearance [1] .", "Within the airways , prolonged residence time of mucus provides a stagnant nidus for c...	[ "Chronic lung infections in cystic fibrosis ( CF ) patients are composed of complex microbial communities that incite persistent inflammation and airway damage .", "Despite the high density of bacteria that colonize the lower airways , nutrient sources that sustain bacterial growth in vivo , and how those nutrien...	[ "Persistent CF lung infections are composed of hundreds of microbial taxa whose interactions contribute to respiratory failure .", "Despite their importance , the complex interplay between the lung microbiota and host environment is poorly understood .", "For example , the nutrients that sustain bacterial growt...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "plant science", "ecology", "plant biology", "molecular biology", "marine and aquatic sciences", "synthetic biology", "biology", "marine biology", "genetics and genomics" ]	How Many Species Are There on Earth and in the Ocean?	journal.pbio.1001127	null	[ [ "Robert May [1] recently noted that if aliens visited our planet , one of their first questions would be , “How many distinct life forms—species—does your planet have ? ”", "He also pointed out that we would be “embarrassed” by the uncertainty in our answer .", "This narrative illustrates the fundamen...	[ "The diversity of life is one of the most striking aspects of our planet; hence knowing how many species inhabit Earth is among the most fundamental questions in science .", "Yet the answer to this question remains enigmatic , as efforts to sample the world's biodiversity to date have been limited and thus have p...	[ "Knowing the number of species on Earth is one of the most basic yet elusive questions in science .", "Unfortunately , obtaining an accurate number is constrained by the fact that most species remain to be described and because indirect attempts to answer this question have been highly controversial .", "Here ,...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "coronary artery disease", "medicine", "genome expression analysis", "cell adhesion", "cell growth", "gene expression", "genetics", "atherosclerosis", "epigenetics", "cardiovascular", "biology", "genomics", "molecular cell biology", "gene networks", "gene function" ]	Alu Elements in ANRIL Non-Coding RNA at Chromosome 9p21 Modulate Atherogenic Cell Functions through Trans-Regulation of Gene Networks	journal.pgen.1003588	null	[ [ "The chromosome 9p21 ( Chr9p21 ) locus is the strongest genetic risk factor of atherosclerosis known today , yet , the responsible mechanisms still remain unclear .", "Chr9p21 lacks associations with common cardiovascular risk factors , such as lipids and hypertension , indicating that the locus exerts it...	[ "The chromosome 9p21 ( Chr9p21 ) locus of coronary artery disease has been identified in the first surge of genome-wide association and is the strongest genetic factor of atherosclerosis known today .", "Chr9p21 encodes the long non-coding RNA ( ncRNA ) antisense non-coding RNA in the INK4 locus ( ANRIL ) .", "...	[ "Chromosome 9p21 is the strongest genetic factor for coronary artery disease and encodes the long non-coding RNA ( ncRNA ) ANRIL .", "Here , we show that increased ANRIL expression mediates atherosclerosis risk through trans-regulation of gene networks leading to pro-atherogenic cellular properties , such as incr...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computer science/natural and synthetic vision", "computational biology/synthetic biology", "computer science/applications", "neuroscience/motor systems", "biophysics/theory and simulation", "computer science/systems and control theory", "computational biology/computational neuroscience", "evolutionar...	Non-Linear Neuronal Responses as an Emergent Property of Afferent Networks: A Case Study of the Locust Lobula Giant Movement Detector	journal.pcbi.1000701	null	[ [ "Since the introduction of the neuron doctrine about 100 years ago , a central question has become what local operations the primitive elements of nervous systems can perform .", "So far , the only operation that has clear experimental support is the threshold operation that converts the depolarization of...	[ "In principle it appears advantageous for single neurons to perform non-linear operations .", "Indeed it has been reported that some neurons show signatures of such operations in their electrophysiological response .", "A particular case in point is the Lobula Giant Movement Detector ( LGMD ) neuron of the locu...	[ "The tiny brains of insects of about 1mm3 smoothly control a flying platform while avoiding obstacles , regulating its distance to objects and search for objects of interest .", "This is largely achieved through a complex hierarchical processing of signals from the multitude of ommatidia in their eye to a set of ...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "mycobacterium leprae", "cell death", "medicine and health sciences", "vesicles", "pathology and laboratory medicine", "intracellular pathogens", "pathogens", "cell processes", "tropical diseases", "macroglial cells", "bacterial diseases", "phagosomes", "schwann cells", "neglected tropical...	The formation of lipid droplets favors intracellular Mycobacterium leprae survival in SW-10, non-myelinating Schwann cells	journal.pntd.0005687	null	[ [ "Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae ( M . leprae ) .", "Although the introduction of multidrug therapy ( MDT ) to leprosy program in 1982 resulted in a significant reduction in the prevalence of the disease , 210 , 758 new lep...	[ "Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae ( M . leprae ) , which is the leading cause of all non-traumatic peripheral neuropathies worldwide .", "Although both myelinating and non-myelinating Schwann cells are infected by M . leprae in pati...	[ "Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae ( M . leprae ) .", "Leprosy is the leading cause of all non-traumatic peripheral neuropathies worldwide .", "Both myelinating and non-myelinating Schwann cells are infected by M . leprae in leprom...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genetic Architecture of Skewed X Inactivation in the Laboratory Mouse	journal.pgen.1003853	null	[ [ "The eutherian female is a mosaic of two cell populations that have either a transcriptionally active maternal or paternal chromosome X . This is a consequence of the mammalian dosage compensation mechanism called X chromosome inactivation ( XCI ) that balances X-linked gene expression between the sexes [1] ....	[ "X chromosome inactivation ( XCI ) is the mammalian mechanism of dosage compensation that balances X-linked gene expression between the sexes .", "Early during female development , each cell of the embryo proper independently inactivates one of its two parental X-chromosomes .", "In mice , the choice of which X...	[ "Although mammalian females have two X chromosomes in each cell , only one is functional , while gene expression from the other is silenced through a process called X chromosome inactivation .", "Little is known about the early stages of this process including how one parental X chromosome is inactivated over the...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "animal diseases", "immune physiology", "enzyme-linked immunoassays", "pathology and laboratory medicine", "diagnostic radiology", "brain damage", "immunology", "brain", "neuroscience", "toxicology", "magnetic resonance imaging", "toxicity", "animal prion di...	Differential Toxicity of Antibodies to the Prion Protein	journal.ppat.1005401	null	[ [ "Active and passive immunotherapy that foster the clearance of pathological aggregates represent potential therapeutic strategies against diseases caused by the inappropriate aggregation of proteins [1] .", "While considerable effort has been devoted to the immunotherapy of Alzheimer's disease with antibo...	[ "Antibodies against the prion protein PrPC can antagonize prion replication and neuroinvasion , and therefore hold promise as possible therapeutics against prion diseases .", "However , the safety profile of such antibodies is controversial .", "It was originally reported that the monoclonal antibody D13 exhibi...	[ "The human prion disease , Creutzfeldt-Jakob disease ( CJD ) , is a progressive neurodegenerative syndrome .", "Although far less prevalent , CJD shows many molecular and clinical similarities to Alzheimer's disease , such as the buildup of protein aggregates in the brain and the absence of effective treatments ....	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "caenorhabditis", "neuronal differentiation", "neuroscience", "animals", "cell differentiation", "motor neurons", "animal models", "developmental biology", "caenorhabditis elegans", "model organisms", "experimental organism systems", "sequence motif analysis", "g protein c...	Unconventional function of an Achaete-Scute homolog as a terminal selector of nociceptive neuron identity	journal.pbio.2004979	null	[ [ "Nervous system development proceeds through sequential steps , starting with the early commitment to a neuronal fate , followed by the progressive restriction of fates , to finally reaching a terminal , differentiated end state .", "Proneural genes of the basic helix-loop-helix ( bHLH ) family play a key...	[ "Proneural genes are among the most early-acting genes in nervous system development , instructing blast cells to commit to a neuronal fate .", "Drosophila Atonal and Achaete-Scute complex ( AS-C ) genes , as well as their vertebrate orthologs , are basic helix-loop-helix ( bHLH ) transcription factors with such ...	[ "Across the animal kingdom , transcription factors of the basic helix-loop-helix ( bHLH ) family act during embryonic nervous system patterning as proneural genes to promote neuroblast identity .", "We describe here a distinct function for a specific member of this family , hlh-4 , in the nematode Caenorhabditis ...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "signal transduction", "molecular cell biology", "biophysic al simulations", "biology", "computational biology" ]	Structural Insights into the Inhibition of Actin-Capping Protein by Interactions with Phosphatidic Acid and Phosphatidylinositol (4,5)-Bisphosphate	journal.pcbi.1002765	null	[ [ "The actin cytoskeleton represents part of a complex network that is essential for cell motility , organelle movements and cell polarity .", "Actin filaments are dynamic structures in general and , in plant cells , they serve as tracks for some of the fastest movements on earth .", "To regulate actin ...	[ "The actin cytoskeleton is a dynamic structure that coordinates numerous fundamental processes in eukaryotic cells .", "Dozens of actin-binding proteins are known to be involved in the regulation of actin filament organization or turnover and many of these are stimulus-response regulators of phospholipid signalin...	[ "The actin cytoskeleton is a prominent feature of eukaryotes and plays a central role in many essential aspects of their lives .", "This highly malleable structure responds to a wide range of stimuli with rapid changes in organization or dynamics .", "These responses are thought to be mediated by dozens of acti...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "genome-wide association studies", "haplotypes", "animal genetics", "mathematics", "statistics (mathematics)", "genetic screens", "genome analysis", "gene identification and analysis", "genetic association studies", "genetics", "biology and life sciences", "population genetics", "physical sc...	A General Approach for Haplotype Phasing across the Full Spectrum of Relatedness	journal.pgen.1004234	null	[ [ "The estimation of haplotypes from SNP genotypes , commonly referred to as ‘phasing’ , is a well studied problem in the literature .", "Existing approaches can be categorised according to the type of cohort each method is designed to phase , and the level of relatedness between the individuals in that coh...	[ "Many existing cohorts contain a range of relatedness between genotyped individuals , either by design or by chance .", "Haplotype estimation in such cohorts is a central step in many downstream analyses .", "Using genotypes from six cohorts from isolated populations and two cohorts from non-isolated population...	[ "Every individual carries two copies of each chromosome ( haplotypes ) , one from each of their parents , that consist of a long sequence of alleles .", "Modern genotyping technologies do not measure haplotypes directly , but the combined sum ( or genotype ) of alleles at each site .", "Statistical methods are ...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/sexually transmitted diseases" ]	Secondary Syphilis in Cali, Colombia: New Concepts in Disease Pathogenesis	journal.pntd.0000690	null	[ [ "Syphilis is a sexually transmitted disease ( STD ) caused by the spirochetal bacterium Treponema pallidum ( Tp ) subspecies pallidum [1] , [2] .", "Despite the existence of inexpensive and effective antibiotic treatment regimens , syphilis continues to be a major public health problem .", "According ...	[ "Venereal syphilis is a multi-stage , sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum ( Tp ) .", "Herein we describe a cohort of 57 patients ( age 18–68 years ) with secondary syphilis ( SS ) identified through a network of public sector primary health care providers in Cali , ...	[ "Venereal syphilis is a sexually transmitted disease caused by the bacterium Treponema pallidum ( Tp ) .", "We describe 57 patients ( age 18–68 years ) from Cali , Colombia diagnosed with secondary syphilis ( SS ) .", "Most were women ( 64 . 9% ) ; predominantly Afro-Colombian ( 38 . 6% ) or mestizo ( 56 . 1% )...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene expression", "infectious diseases/neglected tropical diseases", "molecular biology/mrna stability", "molecular biology", "microbiology", "microbiology/parasitology", "infectious diseases/protozoal infections", "infectious diseases/tropical and travel-associated diseases", ...	Small RNAs with 5′-Polyphosphate Termini Associate with a Piwi-Related Protein and Regulate Gene Expression in the Single-Celled Eukaryote Entamoeba histolytica	journal.ppat.1000219	null	[ [ "Small RNAs mediate post-transcriptional gene silencing in a multitude of organisms and in diverse biological processes [1] , [2] , [3] , [4] , [5] .", "Two proteins central to the small RNA mediated gene silencing pathways are Dicer , an RNaseIII enzyme , which generates small RNAs and Argonaute , which ...	[ "Small interfering RNAs regulate gene expression in diverse biological processes , including heterochromatin formation and DNA elimination , developmental regulation , and cell differentiation .", "In the single-celled eukaryote Entamoeba histolytica , we have identified a population of small RNAs of 27 nt size t...	[ "Regulation of gene expression can occur via multiple conserved pathways .", "One such mechanism is mediated by RNA molecules of about 21–24 nucleotides ( called small RNAs ) , which can affect rates of RNA degradation or protein production .", "These small RNA molecules regulate diverse biological processes in...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "molecular biology/rna-protein interactions", "computational biology/sequence motif analysis" ]	RNAcontext: A New Method for Learning the Sequence and Structure Binding Preferences of RNA-Binding Proteins	journal.pcbi.1000832	null	[ [ "RBPs act in the post-transcriptional regulation ( PTR ) of gene expression by binding to target RNAs to control splicing , stability , localization and translation .", "Recent draft networks of RBP-transcript physical interaction in yeast [1] , fruit flies [2] , and humans [3] reveal a complex and combin...	[ "Metazoan genomes encode hundreds of RNA-binding proteins ( RBPs ) .", "These proteins regulate post-transcriptional gene expression and have critical roles in numerous cellular processes including mRNA splicing , export , stability and translation .", "Despite their ubiquity and importance , the binding prefer...	[ "Many disease-associated mutations do not change the protein sequence of genes; instead they change the instructions on how a gene's mRNA transcript should be processed .", "Translating these instructions allows us to better understand the connection between these mutations and disease .", "RNA-binding proteins...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Hepatitis D Virus Infection of Mice Expressing Human Sodium Taurocholate Co-transporting Polypeptide	journal.ppat.1004840	null	[ [ "Hepatitis D virus ( HDV ) is the smallest virus known to infect humans with a single—stranded , circular RNA genome of about 1 . 7 kilobases in length .", "It is enveloped by surface proteins from its helper hepatitis B virus ( HBV ) and undergoes a unique replication cycle via an intermediate , antigeno...	[ "Hepatitis D virus ( HDV ) is the smallest virus known to infect human .", "About 15 million people worldwide are infected by HDV among those 240 million infected by its helper hepatitis B virus ( HBV ) .", "Viral hepatitis D is considered as one of the most severe forms of human viral hepatitis .", "No speci...	[ "Currently 15 million people worldwide are infected by hepatitis D virus ( HDV ) .", "HDV is the smallest virus known to infect human .", "With co-infection of its helper hepatitis B virus ( HBV ) , viral hepatitis D is considered as the most severe form of viral hepatitis .", "No specific anti-HDV drugs are ...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "rna interference", "mechanisms of signal transduction", "gene regulation", "cloning", "animals", "animal models", "physiological processes", "micrornas", "model organisms", "drosophila melanogaster", "homeostasis", "experimental organism sy...	The bantam microRNA acts through Numb to exert cell growth control and feedback regulation of Notch in tumor-forming stem cells in the Drosophila brain	journal.pgen.1006785	null	[ [ "Balancing self-renewal with differentiation is a key property of all stem cells [1–3] .", "Tipping such balance can have detrimental consequences , resulting in lineage depletion or tumorigenesis .", "N signaling is critically required for lineage homeostasis of both Drosophila and mammalian NSCs [3–...	[ "Notch ( N ) signaling is central to the self-renewal of neural stem cells ( NSCs ) and other tissue stem cells .", "Its deregulation compromises tissue homeostasis and contributes to tumorigenesis and other diseases .", "How N regulates stem cell behavior in health and disease is not well understood .", "Her...	[ "Stem cells are functional units in the development , maintenance , and regeneration of tissues in multicellular organisms .", "Defects in stem cell regulation can compromise tissue homeostasis and result in proliferative or degenerative diseases .", "Our understanding of the molecular and cellular mechanisms r...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "invertebrates", "medicine and health sciences", "reproductive system", "animals", "animal models", "drosophila melanogaster", "model organisms", "x-linked traits", "sequence motif analysis", "molecular biology techniques", "drosophila", "research and analysis method...	Sex Chromosome-wide Transcriptional Suppression and Compensatory Cis-Regulatory Evolution Mediate Gene Expression in the Drosophila Male Germline	journal.pbio.1002499	Expression of sex-linked genes in the Drosophila male germline reflects a balance between an X chromosome-wide transcriptional suppression and long-term, gene-wise evolutionary recruitment of strong, compensatory promoter elements.	[ [ "Heteromorphic sex chromosomes—e . g . , XY males in Drosophila and mammals and ZW females in birds and butterflies—have evolved independently numerous times in animals and in plants [1 , 2] .", "The different chromosome copy numbers between the sexes and the general lack of recombination between X and Y ...	[ "The evolution of heteromorphic sex chromosomes has repeatedly resulted in the evolution of sex chromosome-specific forms of regulation , including sex chromosome dosage compensation in the soma and meiotic sex chromosome inactivation in the germline .", "In the male germline of Drosophila melanogaster , a novel ...	[ "The evolution of different sex chromosomes ( e . g . , X and Y ) has occurred many times in animals and plants .", "One consequence of having different chromosome copy numbers between the sexes ( XY males and XX females ) is the evolution of sex chromosome-specific regulation , both in the soma ( i . e . , X chr...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "gene regulation", "cancers and neoplasms", "vertebrates", "neuroscience", "animals", "epithelial cells", "animal models", "osteichthyes", "oncology", "developmental biology", "model organisms", "stem cells", "experimental organism systems", "chromatophore...	TFAP2 paralogs regulate melanocyte differentiation in parallel with MITF	journal.pgen.1006636	null	[ [ "Melanocytes are responsible for pigment deposition in skin and hair follicles , and the dysregulation of melanocyte differentiation underlies both pigmentation disorders and melanoma .", "Because melanocytes are dispensable for life , the melanocyte lineage can also serve as a model for investigation of ...	[ "Mutations in the gene encoding transcription factor TFAP2A result in pigmentation anomalies in model organisms and premature hair graying in humans .", "However , the pleiotropic functions of TFAP2A and its redundantly-acting paralogs have made the precise contribution of TFAP2-type activity to melanocyte differ...	[ "Identifying the elements and structure of the gene regulatory network governing melanocyte differentiation may yield insight into the mechanisms of pigmentation diseases and melanoma progression .", "Pigmentation is abnormal in Tfap2a mutants , but deciphering the exact role of TFAP2A in the network has been com...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "sequencing techniques", "cell physiology", "medicine and health sciences", "pathology and laboratory medicine", "chemical compounds", "gene regulation", "pathogens", "vibrio", "microbiology", "carbohydrates", "cell metabolism", "organic compounds", "vibrio cholerae", "pharmacology", "mo...	The Vibrio cholerae RND efflux systems impact virulence factor production and adaptive responses via periplasmic sensor proteins	journal.ppat.1006804	null	[ [ "Antimicrobial resistance is an expanding global health threat .", "A ubiquitous mechanism in Gram-negative bacteria that contributes to drug resistance is the ability to reduce antimicrobial uptake .", "Reduced uptake involves decreasing the rate of antimicrobial diffusion across the outer membrane (...	[ "Resistance-nodulation-division ( RND ) efflux systems are ubiquitous transporters in Gram-negative bacteria that are essential for antibiotic resistance .", "The RND efflux systems also contribute to diverse phenotypes independent of antimicrobial resistance , but the mechanism by which they affect most of these...	[ "Multidrug efflux systems belonging to the RND superfamily contribute to the expression of diverse phenotypes in Gram-negative bacteria , but the mechanisms linking RND efflux to these phenotypes is unclear .", "Herein , we provide evidence suggesting that the V . cholerae RND systems influence global transcripti...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "immunology/immunomodulation", "immunology/immune response", "immunology/immunity to infections" ]	Immunity to Lutzomyia intermedia Saliva Modulates the Inflammatory Environment Induced by Leishmania braziliensis	journal.pntd.0000712	null	[ [ "The intracellular protozoan parasites of the Leishmania species are transmitted to vertebrate host through the bites of sand flies .", "Within the vertebrate host , Leishmania parasites reside in phagocytes and induce a spectrum of diseases ranging from a single self-healing cutaneous lesion to the letha...	[ "During blood feeding , sand flies inject Leishmania parasites in the presence of saliva .", "The types and functions of cells present at the first host-parasite contact are critical to the outcome on infection and sand fly saliva has been shown to play an important role in this setting .", "Herein , we investi...	[ "Transmission of Leishmania parasites occurs during blood feeding , when infected female sand flies inject humans with parasites and saliva .", "Chemokines and cytokines are secreted proteins that regulate the initial immune responses and have the potential of attracting and activating cells .", "Herein , we st...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "global health", "infectious disease epidemiology", "epidemiology" ]	Hookworm Infection and Environmental Factors in Mbeya Region, Tanzania: A Cross-Sectional, Population-Based Study	journal.pntd.0002408	null	[ [ "Hookworm disease caused by Ancylostoma duodenale and Necator americanus is among the most common infections in sub-Saharan Africa ( SSA ) and affects up to 198 million people in this region [1]–[3] .", "It causes iron deficiency anemia and protein malnutrition , and has been shown to potentially cause gr...	[ "Hookworm disease is one of the most common infections and cause of a high disease burden in the tropics and subtropics .", "Remotely sensed ecological data and model-based geostatistics have been used recently to identify areas in need for hookworm control .", "Cross-sectional interview data and stool samples ...	[ "Hookworm disease , caused by the nematodes Ancylostoma duodenale and Necator americanus , is an important cause of maternal and child morbidity in the developing countries of the tropics and subtropics .", "In children , hookworm disease has been shown to potentially result in growth retardation as well as intel...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Virus Satellites Drive Viral Evolution and Ecology	journal.pgen.1005609	null	[ [ "Satellites are defined as viruses which have a life cycle dependent on a helper virus , but lack extensive nucleotide sequence homology to the helper virus and are dispensable for helper virus proliferation [1–4] .", "These infectious elements , present both in eukaryotic and prokaryotic cells , have far...	[ "Virus satellites are widespread subcellular entities , present both in eukaryotic and in prokaryotic cells .", "Their modus vivendi involves parasitism of the life cycle of their inducing helper viruses , which assures their transmission to a new host .", "However , the evolutionary and ecological implications...	[ "Satellites are defined as viruses that have a life cycle dependent on a helper virus .", "Thus , they can be considered as parasites of parasites .", "In addition to their fascinating life cycle , these widespread infectious elements , present both in eukaryotic and prokaryotic cells , have a dramatic role in ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "protein metabolism", "protein interactions", "regulatory proteins", "signaling networks", "animal models", "model organisms", "network analysis", "research and analysis methods", "computer and information sciences", "proteins", "regulatory networks", "mouse models", "proteomics", "metabol...	Network Analyses Reveal Pervasive Functional Regulation Between Proteases in the Human Protease Web	journal.pbio.1001869	Network modeling of interactions between proteases and their inhibitors reveals a network of new protein connections and cascades in the protease web.	[ [ "Proteolysis , the hydrolysis of peptide and isopeptide bonds in protein substrates by proteases ( also termed peptidases or proteinases [1] ) , affects every protein at some point during its lifetime .", "The outcomes of proteolysis are of two kinds: Protein degradation ablates protein function by breakd...	[ "Proteolytic processing is an irreversible posttranslational modification affecting a large portion of the proteome .", "Protease-cleaved mediators frequently exhibit altered activity , and biological pathways are often regulated by proteolytic processing .", "Many of these mechanisms have not been appreciated ...	[ "Proteases modify the structure and activity of all proteins by peptide bond hydrolysis and are increasingly recognized as integral regulatory components of numerous biological mechanisms .", "Deregulated protease activity is a common characteristic of many diseases .", "However , protease drug development is c...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "rna", "nucleic acids", "gene expression", "genetics", "gene regulation", "epigenetics", "molecular genetics", "biology", "dna modification", "chromatin", "dna transcription", "histone modification" ]	The Intronic Long Noncoding RNA ANRASSF1 Recruits PRC2 to the RASSF1A Promoter, Reducing the Expression of RASSF1A and Increasing Cell Proliferation	journal.pgen.1003705	null	[ [ "RASSF1A ( RAS-association domain family member 1A ) is a tumor suppressor gene that modulates a broad range of cellular functions essential for normal growth , such as the maintenance of genomic stability , cell cycle control , the modulation of apoptosis , and cell motility and invasion [1] .", "RASSF1A...	[ "The down-regulation of the tumor-suppressor gene RASSF1A has been shown to increase cell proliferation in several tumors .", "RASSF1A expression is regulated through epigenetic events involving the polycomb repressive complex 2 ( PRC2 ) ; however , the molecular mechanisms modulating the recruitment of this epig...	[ "RASSF1A is a tumor suppressor gene whose expression is repressed through epigenetic events in a wide range of different cancers .", "Repression is effected by DNA hypermethylation of the RASSF1A promoter , which in turn is triggered through histone H3K9/H3K27 trimethylation repressive marks .", "The addition o...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "meiosis", "spermatocytes", "cell cycle and cell division", "cell processes", "germ cells", "animal models", "model organisms", "experimental organism systems", "sperm", "research and analysis methods", "specimen preparation and treatment", "staining", "spermatids", "sex chromosomes", "c...	RNF8 and SCML2 cooperate to regulate ubiquitination and H3K27 acetylation for escape gene activation on the sex chromosomes	journal.pgen.1007233	null	[ [ "Worldwide , 15% of couples have difficulty conceiving a child .", "In situations of male infertility , approximately 90% of cases are the result of sperm abnormalities [1] .", "Male infertility is a complex condition with an estimated 15% of cases caused by genetic disorders .", "However , the et...	[ "The sex chromosomes are enriched with germline genes that are activated during the late stages of spermatogenesis .", "Due to meiotic sex chromosome inactivation ( MSCI ) , these sex chromosome-linked genes must escape silencing for activation in spermatids , thereby ensuring their functions for male reproductio...	[ "To produce unimpaired sperm , precise activation of germline-specific genes is an essential step during the late stages of spermatogenesis .", "However , sex chromosomes carrying these genes become silenced in a chromosome-wide manner during meiosis in a process called meiotic sex chromosome inactivation .", "...	2018

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